Exploration of Drug Science

Properties	Small molecules	Stapled peptides	Biologics
Molecular weight	< 1,000	1,000–5,000	> 10,000
Stability	High	High	Low
Binding affinity	Low	High	High
Specificity	Low	High	High
Cellular permeability	High	High	Low
Proteolysis resistance	High	High	Low
Toxicity/side effects	High	Low	Low
Ability to disrupt PPIs	Low	High	High
Manufacturing cost	Low	Low	High

Declarations

Author contributions

QZ and ZW equally contributed to: Conceptualization, Investigation, Writing—original draft, Writing—review & editing. XM: Investigation, Writing—review & editing. QC: Validation, Writing—review & editing, Supervision. CZ: Conceptualization, Writing—original draft, Writing—review & editing, Supervision.

Conflicts of interest

The authors declare that they have no conflicts of interest.

Ethical approval

Not applicable.

Consent to participate

Not applicable.

Consent to publication

Not applicable.

Availability of data and materials

Not applicable.

Funding

Not applicable.

Copyright

References

Wells JA, McClendon CL. Reaching for high-hanging fruit in drug discovery at protein–protein interfaces. Nature. 2007;450:1001–9. [DOI] [PubMed]

Rolland T, Tasan M, Charloteaux B, Pevzner SJ, Zhong Q, Sahni N, et al. A proteome-scale map of the human interactome network. Cell. 2014;159:1212–26. [DOI] [PubMed] [PMC]

Scott DE, Bayly AR, Abell C, Skidmore J. Small molecules, big targets: Drug discovery faces the protein–protein interaction challenge. Nat Rev Drug Discov. 2016;15:533–50. [DOI] [PubMed]

Milroy LG, Grossmann TN, Hennig S, Brunsveld L, Ottmann C. Modulators of protein–protein interactions. Chem Rev. 2014;114:4695–748. [DOI] [PubMed]

Arkin MR, Tang Y, Wells JA. Small-molecule inhibitors of protein-protein interactions: progressing toward the reality. Chem Biol. 2014;21:1102–14. [DOI] [PubMed] [PMC]

Sliwkowski MX, Lofgren JA, Lewis GD, Hotaling TE, Fendly BM, Fox JA. Nonclinical studies addressing the mechanism of action of trastuzumab (herceptin). Semin Oncol. 1999;26:60–70. [PubMed]

Azzarito V, Long K, Murphy NS, Wilson AJ. Inhibition of α-helix-mediated protein–protein interactions using designed molecules. Nat Chem. 2013;5:161–73. [DOI] [PubMed]

Nero TL, Morton CJ, Holien JK, Wielens J, Parker MW. Oncogenic protein interfaces: small molecules, big challenges. Nat Rev Cancer. 2014;14:248–62. [DOI] [PubMed]

Zhao Y, Aguilar A, Bernard D, Wang S. Small-molecule inhibitors of the MDM2–p53 protein–protein interaction (MDM2 inhibitors) in clinical trials for cancer treatment. J Med Chem. 2015;58:1038–52. [DOI] [PubMed] [PMC]

10.

Lazo JS, Sharlow ER. Drugging undruggable molecular cancer targets. Annu Rev Pharmacol Toxicol. 2016;56:23–40. [DOI] [PubMed]

11.

Henley MJ, Koehler AN. Advances in targeting ‘undruggable’ transcription factors with small molecules. Nat Rev Drug Discov. 2021;20:669–88. [DOI] [PubMed]

12.

Zhong L, Li Y, Xiong L, Wang W, Wu M, Yuan T, et al. Small molecules in targeted cancer therapy: advances, challenges, and future perspectives. Signal Transduct Target Ther. 2021;6:201. [DOI] [PubMed] [PMC]

13.

Bakail M, Ochsenbein F. Targeting protein–protein interactions, a wide open field for drug design. C R Chim. 2016;19:19–27. [DOI]

14.

Modi R, McKee N, Zhang N, Alwali A, Nelson S, Lohar A, et al. Stapled peptides as direct inhibitors of Nrf2-sMAF transcription factors. J Med Chem. 2023;66:6184–92. [DOI] [PubMed]

15.

Góngora-Benítez M, Tulla-Puche J, Albericio F. Multifaceted roles of disulfide bonds. Peptides as therapeutics. Chem Rev. 2014;114:901–26. [DOI] [PubMed]

16.

Fosgerau K, Hoffmann T. Peptide therapeutics: current status and future directions. Drug Discov Today. 2015;20:122–8. [DOI] [PubMed]

17.

Nevola L, Giralt E. Modulating protein–protein interactions: the potential of peptides. Chem Commun (Camb). 2015;51:3302–15. [DOI] [PubMed]

18.

Lau JL, Dunn MK. Therapeutic peptides: historical perspectives, current development trends, and future directions. Bioorg Med Chem. 2018;26:2700–7. [DOI] [PubMed]

19.

Muttenthaler M, King GF, Adams DJ, Alewood PF. Trends in peptide drug discovery. Nat Rev Drug Discov. 2021;20:309–25. [DOI] [PubMed]

20.

Philippe GJB, Craik DJ, Henriques ST. Converting peptides into drugs targeting intracellular protein–protein interactions. Drug Discov Today. 2021;26:1521–31. [DOI] [PubMed]

21.

Houk KN, Leach AG, Kim SP, Zhang X. Binding affinities of host–guest, protein–ligand, and protein–transition-state complexes. Angew Chem Int Ed Engl. 2003;42:4872–97. [DOI] [PubMed]

22.

Walensky LD, Bird GH. Hydrocarbon-stapled peptides: principles, practice, and progress. J Med Chem. 2014;57:6275–88. [DOI] [PubMed] [PMC]

23.

Jochim AL, Arora PS. Systematic analysis of helical protein interfaces reveals targets for synthetic inhibitors. ACS Chem Biol. 2010;5:919–23. [DOI] [PubMed] [PMC]

24.

Guarracino DA, Riordan JA, Barreto GM, Oldfield AL, Kouba CM, Agrinsoni D. Macrocyclic control in helix mimetics. Chem Rev. 2019;119:9915–49. [DOI] [PubMed]

25.

Migoń D, Neubauer D, Kamysz W. Hydrocarbon stapled antimicrobial peptides. Protein J. 2018;37:2–12. [DOI] [PubMed] [PMC]

26.

Ali AM, Atmaj J, Van Oosterwijk N, Groves MR, Dömling A. Stapled peptides inhibitors: a new window for target drug discovery. Comput Struct Biotechnol J. 2019;17:263–81. [DOI] [PubMed] [PMC]

27.

Bushweller JH. Targeting transcription factors in cancer — from undruggable to reality. Nat Rev Cancer. 2019;19:611–24. [DOI] [PubMed] [PMC]

28.

Feng M, Jin JQ, Xia L, Xiao T, Mei S, Wang X, et al. Pharmacological inhibition of β-catenin/BCL9 interaction overcomes resistance to immune checkpoint blockades by modulating T_reg cells. Sci Adv. 2019;5:eaau5240. [DOI] [PubMed] [PMC]

29.

Lorion MM, Kaplaneris N, Son J, Kuniyil R, Ackermann L. Late-stage peptide diversification through cobalt-catalyzed C–H activation: sequential multicatalysis for stapled peptides. Angew Chem Int Ed Engl. 2019;58:1684–8. [DOI] [PubMed]

30.

Sharma K, Strizhak AV, Fowler E, Wang X, Xu W, Hatt Jensen C, et al. Water-soluble, stable and azide-reactive strained dialkynes for biocompatible double strain-promoted click chemistry. Org Biomol Chem. 2019;17:8014–8. [DOI] [PubMed]

31.

Saleh MN, Patel MR, Bauer TM, Goel S, Falchook GS, Shapiro GI, et al. Phase 1 trial of ALRN-6924, a dual inhibitor of MDMX and MDM2, in patients with solid tumors and lymphomas bearing wild-type TP53. Clin Cancer Res. 2021;27:5236–47. Erratum in: Clin Cancer Res. 2022;28:429. [DOI] [PubMed] [PMC]

32.

Simov V, Altman MD, Bianchi E, DelRizzo S, DiNunzio EN, Feng G, et al. Discovery and characterization of novel peptide inhibitors of the NRF2/MAFG/DNA ternary complex for the treatment of cancer. Eur J Med Chem. 2021;224:113686. [DOI] [PubMed]

33.

Wu Y, Lu D, Jiang Y, Jin J, Liu S, Chen L, et al. Stapled wasp venom-derived oncolytic peptides with side chains induce rapid membrane lysis and prolonged immune responses in melanoma. J Med Chem. 2021;64:5802–15. [DOI] [PubMed]

34.

Whisenant J, Burgess K. Synthetic helical peptide capping strategies. Chem Soc Rev. 2022;51:5795–804. [DOI] [PubMed]

35.

Bathgate RAD, Praveen P, Sethi A, Furuya WI, Dhingra RR, Kocan M, et al. Noncovalent peptide stapling using alpha-Methyl-L-phenylalanine for α-helical peptidomimetics. J Am Chem Soc. 2023;145:20242–7. [DOI] [PubMed]

36.

Ma B, Liu D, Zheng M, Wang Z, Zhang D, Jian Y, et al. Development of a double-stapled peptide stabilizing both α-helix and β-sheet structures for degrading transcription factor AR-V7. JACS Au. 2024;4:816–27. [DOI] [PubMed] [PMC]

37.

Schafmeister CE, Po J, Verdine GL. An all-hydrocarbon cross-linking system for enhancing the helicity and metabolic stability of peptides. J Am Chem Soc. 2000;122:5891–2. [DOI]

38.

Luong HX, Bui HTP, Tung TT. Application of the all-hydrocarbon stapling technique in the design of membrane-active peptides. J Med Chem. 2022;65:3026–45. [DOI] [PubMed]

39.

Moiola M, Memeo MG, Quadrelli P. Stapled peptides—a useful improvement for peptide-based drugs. Molecules. 2019;24:3654. [DOI] [PubMed] [PMC]

40.

Reguera L, Rivera DG. Multicomponent reaction toolbox for peptide macrocyclization and stapling. Chem Rev. 2019;119:9836–60. [DOI] [PubMed]

41.

Li X, Chen S, Zhang WD, Hu HG. Stapled helical peptides bearing different anchoring residues. Chem Rev. 2020;120:10079–144. [DOI] [PubMed]

42.

Bluntzer MTJ, O’Connell J, Baker TS, Michel J, Hulme AN. Designing stapled peptides to inhibit protein-protein interactions: an analysis of successes in a rapidly changing field. Pept Sci. 2021;113:e24191. [DOI]

43.

Liu J, Wang P, Yan ZQ, Yan JH, Kenry, Zhu Q. Recent advances in late-stage construction of stapled peptides via C–H activation. Chembiochem. 2021;22:2762–71. [DOI] [PubMed]

44.

Tzotzos S. Stapled peptides as potential inhibitors of SARS-CoV-2 binding to the hACE2 receptor. J Pept Sci. 2022;28:e3409. [DOI] [PubMed] [PMC]

45.

Lau YH, de Andrade P, Wu Y, Spring DR. Peptide stapling techniques based on different macrocyclisation chemistries. Chem Soc Rev. 2015;44:91–102. [DOI] [PubMed]

46.

Lau YH, Wu Y, Rossmann M, Tan BX, de Andrade P, Tan YS, et al. Double strain-promoted macrocyclization for the rapid selection of cell-active stapled peptides. Angew Chem Int Ed Engl. 2015;54:15410–3. [DOI] [PubMed] [PMC]

47.

Wu Y, Villa F, Maman J, Lau YH, Dobnikar L, Simon AC, et al. Targeting the genome-stability hub Ctf4 by stapled-peptide design. Angew Chem Int Ed Engl. 2017;56:12866–72. [DOI] [PubMed]

48.

Guo Y, Fu L, Fan X, Shi X. Stapled SC34EK fusion inhibitors with high potency against HIV-1 and improved protease resistance. Chin Chem Lett. 2018;29:1167–70. [DOI]

49.

Rezaei Araghi R, Bird GH, Ryan JA, Jenson JM, Godes M, Pritz JR, et al. Iterative optimization yields Mcl-1–targeting stapled peptides with selective cytotoxicity to Mcl-1–dependent cancer cells. Proc Natl Acad Sci U S A. 2018;115:E886–95. [DOI] [PubMed] [PMC]

50.

Gallagher EE, Song JM, Menon A, Mishra LD, Chmiel AF, Garner AL. Consideration of binding kinetics in the design of stapled peptide mimics of the disordered proteins eukaryotic translation initiation factor 4E-binding protein 1 and eukaryotic translation initiation factor 4G. J Med Chem. 2019;62:4967–78. [DOI] [PubMed] [PMC]

51.

Kannan S, Aronica PGA, Tan YS, Verma CS. Inhibiting S100B(ββ) for activating wild-type p53: design of stapled peptides. ACS Omega. 2019;4:5335–44. [DOI]

52.

Song JM, Gallagher EE, Menon A, Mishra LD, Garner AL. The role of olefin geometry in the activity of hydrocarbon stapled peptides targeting eukaryotic translation initiation factor 4E (eIF4E). Org Biomol Chem. 2019;17:6414–9. [DOI] [PubMed] [PMC]

53.

Verhoork SJM, Jennings CE, Rozatian N, Reeks J, Meng J, Corlett EK, et al. Tuning the binding affinity and selectivity of perfluoroaryl-stapled peptides by cysteine-editing. Chemistry. 2019;25:177–82. [DOI] [PubMed]

54.

Wang J, Zhang J, Sun X, Liu C, Li X, Chen L. Molecular design of sequence-minimized, structure-optimized, and hydrocarbon-stapled helix–helix interactions in the trimer-of-hairpins motif of pediatric pneumonia RSV-F protein. Chem Biol Drug Des. 2019;94:1292–9. [DOI] [PubMed]

55.

Hetherington K, Hegedus Z, Edwards TA, Sessions RB, Nelson A, Wilson AJ. Stapled peptides as HIF-1α/p300 inhibitors: helicity enhancement in the bound state increases inhibitory potency. Chemistry. 2020;26:7638–46. [DOI] [PubMed] [PMC]

56.

Sharma K, Strizhak AV, Fowler E, Xu W, Chappell B, Sore HF, et al. Functionalized double strain-promoted stapled peptides for inhibiting the p53-MDM2 interaction. ACS Omega. 2020;5:1157–69. [DOI] [PubMed] [PMC]

57.

de Campos LJ, Palermo NY, Conda-Sheridan M. Targeting SARS-CoV-2 receptor binding domain with stapled peptides: an in silico study. J Phys Chem B. 2021;125:6572–86. [DOI] [PubMed]

58.

Hart P’, Hommen P, Noisier A, Krzyzanowski A, Schüler D, Porfetye AT, et al. Structure based design of bicyclic peptide inhibitors of RbAp48. Angew Chem Int Ed Engl. 2021;60:1813–20. [DOI] [PubMed] [PMC]

59.

Maas MN, Hintzen JCJ, Löffler PMG, Mecinović J. Targeting SARS-CoV-2 spike protein by stapled hACE2 peptides. Chem Commun (Camb). 2021;57:3283–6. [DOI] [PubMed]

60.

Schmeing S, Amrahova G, Bigler K, Chang JY, Openy J, Pal S, et al. Rationally designed stapled peptides allosterically inhibit PTBP1–RNA-binding. Chem Sci. 2023;14:8269–78. [DOI] [PubMed] [PMC]

61.

Mendive-Tapia L, Preciado S, García J, Ramón R, Kielland N, Albericio F, et al. New peptide architectures through C–H activation stapling between tryptophan–phenylalanine/tyrosine residues. Nat Commun. 2015;6:7160. [DOI] [PubMed] [PMC]

62.

Cai X, Zheng W, Shi X, Chen L, Liu Z, Li Z. HBx-derived constrained peptides inhibit the secretion of hepatitis B virus antigens. Mol Pharm. 2018;15:5646–52. [DOI] [PubMed]

63.

Li Y, Wu M, Chang Q, Zhao X. Stapling strategy enables improvement of antitumor activity and proteolytic stability of host-defense peptide hymenochirin-1B. RSC Adv. 2018;8:22268–75. [DOI] [PubMed] [PMC]

64.

Speltz TE, Mayne CG, Fanning SW, Siddiqui Z, Tajkhorshid E, Greene GL, et al. A “cross-stitched” peptide with improved helicity and proteolytic stability. Org Biomol Chem. 2018;16:3702–6. [DOI] [PubMed] [PMC]

65.

Partridge AW, Kaan HYK, Juang YC, Sadruddin A, Lim S, Brown CJ, et al. Incorporation of putative helix-breaking amino acids in the design of novel stapled peptides: exploring biophysical and cellular permeability properties. Molecules. 2019;24:2292. [DOI] [PubMed] [PMC]

66.

Pflimlin E, Lear S, Lee C, Yu S, Zou H, To A, et al. Design of a long-acting and selective MEG-fatty acid stapled prolactin-releasing peptide analog. ACS Med Chem Lett. 2019;10:1166–72. [DOI] [PubMed] [PMC]

67.

Robertson NS, Walsh SJ, Fowler E, Yoshida M, Rowe SM, Wu Y, et al. Macrocyclisation and functionalisation of unprotected peptides via divinyltriazine cysteine stapling. Chem Commun (Camb). 2019;55:9499–502. [DOI] [PubMed]

68.

Hawley KM, Eclov RJ, Schnorenberg MR, Tian Y, Shah RN, Thomas-Toth AT, et al. Inhibition of FOXP3 by stapled alpha-helical peptides dampens regulatory T cell function. Proc Natl Acad Sci U S A. 2022;119:e2209044119. [DOI] [PubMed] [PMC]

69.

Baek S, Kutchukian PS, Verdine GL, Huber R, Holak TA, Lee KW, et al. Structure of the stapled p53 peptide bound to Mdm2. J Am Chem Soc. 2012;134:103–6. [DOI] [PubMed]

70.

Diderich P, Bertoldo D, Dessen P, Khan MM, Pizzitola I, Held W, et al. Phage selection of chemically stabilized α-helical peptide ligands. ACS Chem Biol. 2016;11:1422–7. [DOI] [PubMed]

71.

Quagliata M, Stincarelli MA, Papini AM, Giannecchini S, Rovero P. Antiviral activity against SARS-CoV-2 of conformationally constrained helical peptides derived from angiotensin-converting enzyme 2. ACS Omega. 2023;8:22665–72. [DOI] [PubMed] [PMC]

72.

Moellering RE, Cornejo M, Davis TN, Del Bianco C, Aster JC, Blacklow SC, et al. Direct inhibition of the NOTCH transcription factor complex. Nature. 2009;462:182–8. Erratum in: Nature. 2010;463:384. [DOI] [PubMed] [PMC]

73.

Weng AP, Ferrando AA, Lee W, Morris JP 4th, Silverman LB, Sanchez-Irizarry C, et al. Activating mutations of NOTCH1 in human T cell acute lymphoblastic leukemia. Science. 2004;306:269–71. [DOI] [PubMed]

74.

Nam Y, Sliz P, Song L, Aster JC, Blacklow SC. Structural basis for cooperativity in recruitment of MAML coactivators to Notch transcription complexes. Cell. 2006;124:973–83. [DOI] [PubMed]

75.

Diviani D, Raimondi F, Del Vescovo CD, Dreyer E, Reggi E, Osman H, et al. Small-molecule protein-protein interaction inhibitor of oncogenic Rho signaling. Cell Chem Biol. 2016;23:1135–46. [DOI] [PubMed]

76.

Wu T, He P, Wu W, Chen Y, Lv F. Targeting oncogenic transcriptional corepressor Nac1 POZ domain with conformationally constrained peptides by cyclization and stapling. Bioorg Chem. 2018;80:1–10. [DOI] [PubMed]

77.

Wang L, Song Y, Wang H, Zhang X, Wang M, He J, et al. Advances of artificial intelligence in anti-cancer drug design: a review of the past decade. Pharmaceuticals (Basel). 2023;16:253. [DOI] [PubMed] [PMC]

78.

Lu Y, Li Z, Zhang S, Zhang T, Liu Y, Zhang L. Cellular mitophagy: mechanism, roles in diseases and small molecule pharmacological regulation. Theranostics. 2023;13:736–66. [DOI] [PubMed] [PMC]

79.

Jumper J, Evans R, Pritzel A, Green T, Figurnov M, Ronneberger O, et al. Highly accurate protein structure prediction with AlphaFold. Nature. 2021;596:583–9. [DOI] [PubMed] [PMC]

80.

Diller DJ, Swanson J, Bayden AS, Brown CJ, Thean D, Lane DP, et al. Rigorous computational and experimental investigations on MDM2/MDMX-targeted linear and macrocyclic peptides. Molecules. 2019;24:4586. [DOI] [PubMed] [PMC]

81.

Limaye AJ, Bendzunas GN, Whittaker MK, LeClair TJ, Helton LG, Kennedy EJ. In silico optimized stapled peptides targeting WASF3 in breast cancer. ACS Med Chem Lett. 2022;13:570–6. [DOI] [PubMed] [PMC]

82.

Hossain MA, Guilhaudis L, Sonnevend A, Attoub S, van Lierop BJ, Robinson AJ, et al. Synthesis, conformational analysis and biological properties of a dicarba derivative of the antimicrobial peptide, brevinin-1BYa. Eur Biophys J. 2011;40:555–64. [DOI] [PubMed]

83.

Kim YW, Kutchukian PS, Verdine GL. Introduction of all-hydrocarbon i,i+3 staples into α-helices via ring-closing olefin metathesis. Org Lett. 2010;12:3046–9. [DOI] [PubMed]

84.

Jeganathan S, Wendt M, Kiehstaller S, Brancaccio D, Kuepper A, Pospiech N, et al. Constrained peptides with fine-tuned flexibility inhibit NF-Y transcription factor assembly. Angew Chem Int Ed Engl. 2019;58:17351–8. [DOI] [PubMed] [PMC]

85.

Bird GH, Fu A, Escudero S, Godes M, Opoku-Nsiah K, Wales TE, et al. Hydrocarbon-stitched peptide agonists of glucagon-like peptide-1 receptor. ACS Chem Biol. 2020;15:1340–8. [DOI] [PubMed] [PMC]

86.

Mookherjee N, Anderson MA, Haagsman HP, Davidson DJ. Antimicrobial host defence peptides: functions and clinical potential. Nat Rev Drug Discov. 2020;19:311–32. [DOI] [PubMed]

87.

Mourtada R, Herce HD, Yin DJ, Moroco JA, Wales TE, Engen JR, et al. Design of stapled antimicrobial peptides that are stable, nontoxic and kill antibiotic-resistant bacteria in mice. Nat Biotechnol. 2019;37:1186–97. [DOI] [PubMed] [PMC]

88.

Yang Q, Qiu X, Zhang X, Yu Y, Li N, Wei X, et al. Optimization of beclin 1-targeting stapled peptides by staple scanning leads to enhanced antiproliferative potency in cancer cells. J Med Chem. 2021;64:13475–86. [DOI] [PubMed]

89.

Blackwell HE, Grubbs RH. Highly efficient synthesis of covalently cross-linked peptide helices by ring-closing metathesis. Angew Chem Int Ed Engl. 1998;37:3281–4. [DOI] [PubMed]

90.

Walensky LD, Kung AL, Escher I, Malia TJ, Barbuto S, Wright RD, et al. Activation of apoptosis in vivo by a hydrocarbon-stapled BH3 helix. Science. 2004;305:1466–70. [DOI] [PubMed] [PMC]

91.

Hossain MA, Haugaard-Kedström LM, Rosengren KJ, Bathgate RA, Wade JD. Chemically synthesized dicarba H2 relaxin analogues retain strong RXFP1 receptor activity but show an unexpected loss of in vitro serum stability. Org Biomol Chem. 2015;13:10895–903. [DOI] [PubMed]

92.

Hossain MA, Rosengren KJ, Zhang S, Bathgate RAD, Tregear GW, van Lierop BJ, et al. Solid phase synthesis and structural analysis of novel A-chain dicarba analogs of human relaxin-3 (INSL7) that exhibit full biological activity. Org Biomol Chem. 2009;7:1547–53. [DOI] [PubMed]

93.

Jackson DY, King DS, Chmielewski J, Singh S, Schultz PG. General approach to the synthesis of short α-helical peptides. J Am Chem Soc. 1991;113:9391–2. [DOI]

94.

Ravi A, Prasad BVV, Balaram P. Cyclic peptide disulfides. Solution and solid-state conformation of Boc-Cys-Pro-Aib-Cys-NHMe with a disulfide bridge from Cys to Cys, a disulfide-bridged peptide helix. J Am Chem Soc. 1983;105:105–9. [DOI]

95.

Pace JR, Lampkin BJ, Abakah C, Moyer A, Miao J, Deprey K, et al. Stapled β-hairpins featuring 4-mercaptoproline. J Am Chem Soc. 2021;143:15039–44. [DOI] [PubMed] [PMC]

96.

Fairlie DP, Dantas de Araujo A. Review stapling peptides using cysteine crosslinking. Biopolymers. 2016;106:843–52. [DOI] [PubMed]

97.

Paterson DL, Flanagan JU, Shepherd PR, Harris PWR, Brimble MA. Variable-length ester-based staples for α-helical peptides by using a double thiol-ene reaction. Chemistry. 2020;26:10826–33. [DOI] [PubMed]

98.

Peraro L, Zou Z, Makwana KM, Cummings AE, Ball HL, Yu H, et al. Diversity-oriented stapling yields intrinsically cell-penetrant inducers of autophagy. J Am Chem Soc. 2017;139:7792–802. [DOI] [PubMed] [PMC]

99.

Brown SP, Smith AB 3rd. Peptide/protein stapling and unstapling: introduction of s-tetrazine, photochemical release, and regeneration of the peptide/protein. J Am Chem Soc. 2015;137:4034–7. [DOI] [PubMed] [PMC]

100.

Assem N, Ferreira DJ, Wolan DW, Dawson PE. Acetone-linked peptides: a convergent approach for peptide macrocyclization and labeling. Angew Chem Int Ed Engl. 2015;54:8665–8. [DOI] [PubMed] [PMC]

101.

Felix AM, Heimer EP, Wang CT, Lambros TJ, Fournier A, Mowles TF, et al. Synthesis, biological activity and conformational analysis of cyclic GRF analogs. Int J Pept Protein Res. 1988;32:441–54. [DOI] [PubMed]

102.

Taylor JW. The synthesis and study of side-chain lactam-bridged peptides. Biopolymers. 2002;66:49–75. [DOI] [PubMed]

103.

Wegener KL, McGrath AE, Dixon NE, Oakley AJ, Scanlon DB, Abell AD, et al. Rational design of a 3₁₀-helical PIP-box mimetic targeting PCNA, the human sliding clamp. Chemistry. 2018;24:11325–31. [DOI] [PubMed]

104.

Shepherd NE, Hoang HN, Abbenante G, Fairlie DP. Single turn peptide alpha helices with exceptional stability in water. J Am Chem Soc. 2005;127:2974–83. [DOI] [PubMed]

105.

Skowron KJ, Speltz TE, Moore TW. Recent structural advances in constrained helical peptides. Med Res Rev. 2019;39:749–70. [DOI] [PubMed] [PMC]

106.

Sletten EM, Bertozzi CR. Bioorthogonal chemistry: fishing for selectivity in a sea of functionality. Angew Chem Int Ed Engl. 2009;48:6974–98. [DOI] [PubMed] [PMC]

107.

Lau YH, Wu Y, de Andrade P, Galloway WR, Spring DR. A two-component ‘double-click’ approach to peptide stapling. Nat Protoc. 2015;10:585–94. [DOI] [PubMed]

108.

Lau YH, de Andrade P, Quah ST, Rossmann M, Laraia L, Sköld N, et al. Functionalised staple linkages for modulating the cellular activity of stapled peptides. Chem Sci. 2014;5:1804–9. [DOI]

109.

Xu W, Lau YH, Fischer G, Tan YS, Chattopadhyay A, de la Roche M, et al. Macrocyclized extended peptides: inhibiting the substrate-recognition domain of tankyrase. J Am Chem Soc. 2017;139:2245–56. [DOI] [PubMed] [PMC]

110.

Wu Y, Kaur A, Fowler E, Wiedmann MM, Young R, Galloway WRJD, et al. Toolbox of diverse linkers for navigating the cellular efficacy landscape of stapled peptides. ACS Chem Biol. 2019;14:526–33. [DOI] [PubMed]

111.

Li B, Tang H, Turlik A, Wan Z, Xue XS, Li L, et al. Cooperative stapling of native peptides at lysine and tyrosine or arginine with formaldehyde. Angew Chem Int Ed Engl. 2021;60:6646–52. [DOI] [PubMed]

112.

Maity A, Choudhury AR, Chakrabarti R. Effect of stapling on the thermodynamics of mdm2–p53 binding. J Chem Inf Model. 2021;61:1989–2000. [DOI] [PubMed]

113.

Bernal F, Tyler AF, Korsmeyer SJ, Walensky LD, Verdine GL. Reactivation of the p53 tumor suppressor pathway by a stapled p53 peptide. J Am Chem Soc. 2007;129:2456–7. Erratum in: J Am Chem Soc. 2007;129:5298. [DOI] [PubMed] [PMC]

114.

Kannan S, Partridge AW, Lane DP, Verma CS. The dual interactions of p53 with MDM2 and p300: implications for the design of MDM2 inhibitors. Int J Mol Sci. 2019;20:5996. [DOI] [PubMed] [PMC]

115.

Cathcart AM, Bird GH, Wales TE, Herce HD, Harvey EP, Hauseman ZJ, et al. Targeting a helix-in-groove interaction between E1 and E2 blocks ubiquitin transfer. Nat Chem Biol. 2020;16:1218–26. [DOI] [PubMed] [PMC]

116.

Morgan DC, Morris C, Mahindra A, Blair CM, Tejeda G, Herbert I, et al. Stapled ACE2 peptidomimetics designed to target the SARS-CoV-2 spike protein do not prevent virus internalization. Pept Sci (Hoboken). 2021;113:e24217. [DOI] [PubMed] [PMC]

117.

Zheng M, Cong W, Peng H, Qing J, Shen H, Tang Y, et al. Stapled peptides targeting SARS-CoV-2 spike protein HR1 inhibit the fusion of virus to its cell receptor. J Med Chem. 2021;64:17486–95. [DOI] [PubMed]

118.

Choudhury AR, Maity A, Chakraborty S, Chakrabarti R. Computational design of stapled peptide inhibitor against SARS-CoV-2 receptor binding domain. Pept Sci (Hoboken). 2022;114:e24267. [DOI] [PubMed] [PMC]

119.

Lai Y, Fois G, Flores JR, Tuvim MJ, Zhou Q, Yang K, et al. Inhibition of calcium-triggered secretion by hydrocarbon-stapled peptides. Nature. 2022;603:949–56. [DOI] [PubMed] [PMC]

120.

Montgomery JE, Donnelly JA, Fanning SW, Speltz TE, Shangguan X, Coukos JS, et al. Versatile peptide macrocyclization with Diels–Alder cycloadditions. J Am Chem Soc. 2019;141:16374–81. [DOI] [PubMed] [PMC]

121.

Wang Y, Chou DH. A thiol–ene coupling approach to native peptide stapling and macrocyclization. Angew Chem Int Ed Engl. 2015;54:10931–4. [DOI] [PubMed]

122.

Islam MS, Junod SL, Zhang S, Buuh ZY, Guan Y, Zhao M, et al. Unprotected peptide macrocyclization and stapling via a fluorine-thiol displacement reaction. Nat Commun. 2022;13:350. [DOI] [PubMed] [PMC]

123.

Anananuchatkul T, Chang IV, Miki T, Tsutsumi H, Mihara H. Construction of a stapled α-helix peptide library displayed on phage for the screening of galectin-3-binding peptide ligands. ACS Omega. 2020;5:5666–74. [DOI] [PubMed] [PMC]

124.

Tian Y, Jiang Y, Li J, Wang D, Zhao H, Li Z. Effect of stapling architecture on physiochemical properties and cell permeability of stapled α-helical peptides: a comparative study. Chembiochem. 2017;18:2087–93. [DOI] [PubMed]

125.

Spokoyny AM, Zou Y, Ling JJ, Yu H, Lin YS, Pentelute BL. A perfluoroaryl-cysteine S_NAr chemistry approach to unprotected peptide stapling. J Am Chem Soc. 2013;135:5946–9. [DOI] [PubMed] [PMC]

126.

Ngambenjawong C, Pineda JM, Pun SH. Engineering an affinity-enhanced peptide through optimization of cyclization chemistry. Bioconjug Chem. 2016;27:2854–62. [DOI] [PubMed] [PMC]

127.

Kumita JR, Smart OS, Woolley GA. Photo-control of helix content in a short peptide. Proc Natl Acad Sci U S A. 2000;97:3803–8. [DOI] [PubMed] [PMC]

128.

White AM, Dellsén A, Larsson N, Kaas Q, Jansen F, Plowright AT, et al. Late-stage functionalization with cysteine staples generates potent and selective melanocortin receptor-1 agonists. J Med Chem. 2022;65:12956–69. [DOI] [PubMed]

129.

Chen KE, Guo Q, Hill TA, Cui Y, Kendall AK, Yang Z, et al. De novo macrocyclic peptides for inhibiting, stabilizing, and probing the function of the retromer endosomal trafficking complex. Sci Adv. 2021;7:eabg4007. [DOI] [PubMed] [PMC]

130.

Helton LG, Soliman A, von Zweydorf F, Kentros M, Manschwetus JT, Hall S, et al. Allosteric inhibition of Parkinson’s-linked LRRK2 by constrained peptides. ACS Chem Biol. 2021;16:2326–38. [DOI] [PubMed]

131.

Speltz TE, Qiao Z, Swenson CS, Shangguan X, Coukos JS, Lee CW, et al. Targeting MYC with modular synthetic transcriptional repressors derived from bHLH DNA-binding domains. Nat Biotechnol. 2023;41:541–51. [DOI] [PubMed] [PMC]

132.

Rezaei Araghi R, Ryan JA, Letai A, Keating AE. Rapid optimization of Mcl-1 inhibitors using stapled peptide libraries including non-natural side chains. ACS Chem Biol. 2016;11:1238–44. [DOI] [PubMed] [PMC]

133.

Wu S, He Y, Qiu X, Yang W, Liu W, Li X, et al. Targeting the potent beclin 1–UVRAG coiled-coil interaction with designed peptides enhances autophagy and endolysosomal trafficking. Proc Natl Acad Sci U S A. 2018;115:E5669–78. [DOI] [PubMed] [PMC]

134.

Brown H, Chung M, Üffing A, Batistatou N, Tsang T, Doskocil S, et al. Structure-based design of stapled peptides that bind GABARAP and inhibit autophagy. J Am Chem Soc. 2022;144:14687–97. [DOI] [PubMed] [PMC]

135.

Cui J, Ogasawara Y, Kurata I, Matoba K, Fujioka Y, Noda NN, et al. Targeting the ATG5-ATG16L1 protein–protein interaction with a hydrocarbon-stapled peptide derived from ATG16L1 for autophagy inhibition. J Am Chem Soc. 2022;144:17671–9. [DOI] [PubMed]

136.

Mayer G, Shpilt Z, Kowalski H, Tshuva EY, Friedler A. Targeting protein interaction hotspots using structured and disordered chimeric peptide inhibitors. ACS Chem Biol. 2022;17:1811–23. [DOI] [PubMed]

137.

Ricardo MG, Ali AM, Plewka J, Surmiak E, Labuzek B, Neochoritis CG, et al. Multicomponent peptide stapling as a diversity-driven tool for the development of inhibitors of protein–protein interactions. Angew Chem Int Ed Engl. 2020;59:5235–41. [DOI] [PubMed]

138.

Ye X, Lee YC, Gates ZP, Ling Y, Mortensen JC, Yang FS, et al. Binary combinatorial scanning reveals potent poly-alanine-substituted inhibitors of protein-protein interactions. Commun Chem. 2022;5:128. [DOI] [PubMed] [PMC]

139.

Paquette AR, Payne SR, McKay GA, Brazeau-Henrie JT, Darnowski MG, Kammili A, et al. RpoN-based stapled peptides with improved DNA binding suppress Pseudomonas aeruginosa virulence. RSC Med Chem. 2022;13:445–55. [DOI] [PubMed] [PMC]

140.

Learte-Aymamí S, Martin-Malpartida P, Roldán-Martín L, Sciortino G, Couceiro JR, Maréchal JD, et al. Controlling oncogenic KRAS signaling pathways with a palladium-responsive peptide. Commun Chem. 2022;5:75. [DOI] [PubMed] [PMC]

141.

Zhang G, Barragan F, Wilson K, Levy N, Herskovits A, Sapozhnikov M, et al. A solid-phase approach to accessing bisthioether-stapled peptides resulting in a potent inhibitor of PRC2 catalytic activity. Angew Chem Int Ed Engl. 2018;57:17073–8. [DOI] [PubMed]

142.

Yang PY, Zou H, Lee C, Muppidi A, Chao E, Fu Q, et al. Stapled, long-acting glucagon-like peptide 2 analog with efficacy in dextran sodium sulfate induced mouse colitis models. J Med Chem. 2018;61:3218–23. [DOI] [PubMed]

143.

Meng G, Pu J, Li Y, Han A, Tian Y, Xu W, et al. Design and biological evaluation of m-xylene thioether-stapled short helical peptides targeting the HIV-1 gp41 hexameric coiled–coil fusion complex. J Med Chem. 2019;62:8773–83. [DOI] [PubMed]

144.

Bellavita R, Casciaro B, Di Maro S, Brancaccio D, Carotenuto A, Falanga A, et al. First-in-class cyclic temporin L analogue: design, synthesis, and antimicrobial assessment. J Med Chem. 2021;64:11675–94. [DOI] [PubMed] [PMC]

145.

Curreli F, Victor SMB, Ahmed S, Drelich A, Tong X, Tseng CK, et al. Stapled peptides based on human angiotensin-converting enzyme 2 (ACE2) potently inhibit SARS-CoV-2 infection in vitro. mBio. 2020;11:e02451-20. [DOI] [PubMed] [PMC]

146.

Takyo M, Sato Y, Hirata N, Tsuchiya K, Ishida H, Kurohara T, et al. Oligoarginine-conjugated peptide foldamers inhibiting vitamin d receptor-mediated transcription. ACS Omega. 2022;7:46573–82. [DOI] [PubMed] [PMC]

147.

Adak A, Das G, Gupta V, Khan J, Mukherjee N, Mondal P, et al. Evolution of potential antimitotic stapled peptides from multiple helical peptide stretches of the tubulin heterodimer interface: helix-mimicking stapled peptide tubulin inhibitors. J Med Chem. 2022;65:13866–78. [DOI] [PubMed]

148.

Kuster A, Mozaffari NL, Wilkinson OJ, Wojtaszek JL, Zurfluh C, Przetocka S, et al. A stapled peptide mimetic of the CtIP tetramerization motif interferes with double-strand break repair and replication fork protection. Sci Adv. 2021;7:eabc6381. [DOI] [PubMed] [PMC]

149.

Yang Y, Lee C, Reddy RR, Huang DJ, Zhong W, Nguyen-Tran VTB, et al. Design of potent and proteolytically stable biaryl-stapled GLP-1R/GIPR peptide dual agonists. ACS Chem Biol. 2022;17:1249–58. [DOI] [PubMed] [PMC]

150.

Li Y, Zhang Y, Wu M, Chang Q, Hu H, Zhao X. Improving selectivity, proteolytic stability, and antitumor activity of hymenochirin-1B: a novel glycosylated staple strategy. ACS Chem Biol. 2019;14:516–25. [DOI] [PubMed]

151.

Bird GH, Madani N, Perry AF, Princiotto AM, Supko JG, He X, et al. Hydrocarbon double-stapling remedies the proteolytic instability of a lengthy peptide therapeutic. Proc Natl Acad Sci U S A. 2010;107:14093–8. [DOI] [PubMed] [PMC]

152.

Grossmann TN, Yeh JT, Bowman BR, Chu Q, Moellering RE, Verdine GL. Inhibition of oncogenic Wnt signaling through direct targeting of β-catenin. Proc Natl Acad Sci U S A. 2012;109:17942–7. [DOI] [PubMed] [PMC]

153.

Chandramohan A, Josien H, Yuen TY, Duggal R, Spiegelberg D, Yan L, et al. Design-rules for stapled peptides with in vivo activity and their application to Mdm2/X antagonists. Nat Commun. 2024;15:489. [DOI] [PubMed] [PMC]

154.

Muppidi A, Doi K, Ramil CP, Wang HG, Lin Q. Synthesis of cell-permeable stapled BH3 peptide-based Mcl-1 inhibitors containing simple aryl and vinylaryl cross-linkers. Tetrahedron. 2014;70:7740–5. [DOI] [PubMed] [PMC]

155.

Wang Y, Ho TG, Franz E, Hermann JS, Smith FD, Hehnly H, et al. PKA-type I selective constrained peptide disruptors of AKAP complexes. ACS Chem Biol. 2015;10:1502–10. [DOI] [PubMed] [PMC]

156.

Li S, Zhang X, Guo C, Peng Y, Liu X, Wang B, et al. Hydrocarbon staple constructing highly efficient α-helix cell-penetrating peptides for intracellular cargo delivery. Chem Commun (Camb). 2020;56:15655–8. [DOI] [PubMed]

157.

Sakagami K, Masuda T, Kawano K, Futaki S. Importance of net hydrophobicity in the cellular uptake of all-hydrocarbon stapled peptides. Mol Pharm. 2018;15:1332–40. [DOI] [PubMed]

158.

Hirano M, Yokoo H, Goto C, Oba M, Misawa T, Demizu Y. Magainin 2-derived stapled peptides derived with the ability to deliver pDNA, mRNA, and siRNA into cells. Chem Sci. 2023;14:10403–10. [DOI] [PubMed] [PMC]

159.

Moerke NJ, Aktas H, Chen H, Cantel S, Reibarkh MY, Fahmy A, et al. Small-molecule inhibition of the interaction between the translation initiation factors eIF4E and eIF4G. Cell. 2007;128:257–67. [DOI] [PubMed]

160.

Lama D, Liberatore AM, Frosi Y, Nakhle J, Tsomaia N, Bashir T, et al. Structural insights reveal a recognition feature for tailoring hydrocarbon stapled-peptides against the eukaryotic translation initiation factor 4E protein. Chem Sci. 2019;10:2489–500. [DOI] [PubMed] [PMC]

161.

Song JM, Menon A, Mitchell DC, Johnson OT, Garner AL. High-throughput chemical probing of full-length protein–protein interactions. ACS Comb Sci. 2017;19:763–9. [DOI] [PubMed] [PMC]

162.

Gallagher EE, Menon A, Chmiel AF, Deprey K, Kritzer JA, Garner AL. A cell-penetrant lactam-stapled peptide for targeting eIF4E protein-protein interactions. Eur J Med Chem. 2020;205:112655. [DOI] [PubMed] [PMC]

163.

Bird GH, Mazzola E, Opoku-Nsiah K, Lammert MA, Godes M, Neuberg DS, et al. Biophysical determinants for cellular uptake of hydrocarbon-stapled peptide helices. Nat Chem Biol. 2016;12:845–52. [DOI] [PubMed] [PMC]

164.

Guidotti G, Brambilla L, Rossi D. Cell-penetrating peptides: from basic research to clinics. Trends Pharmacol Sci. 2017;38:406–24. [DOI] [PubMed]

165.

Speltz TE, Danes JM, Stender JD, Frasor J, Moore TW. A cell-permeable stapled peptide inhibitor of the estrogen receptor/coactivator interaction. ACS Chem Biol. 2018;13:676–84. [DOI] [PubMed] [PMC]

166.

Xu J, Khan AR, Fu M, Wang R, Ji J, Zhai G. Cell-penetrating peptide: a means of breaking through the physiological barriers of different tissues and organs. J Control Release. 2019;309:106–24. [DOI] [PubMed]

167.

Peraro L, Kritzer JA. Emerging methods and design principles for cell-penetrant peptides. Angew Chem Int Ed Engl. 2018;57:11868–81. [DOI] [PubMed] [PMC]

168.

Chu Q, Moellering RE, Hilinski GJ, Kim YW, Grossmann TN, Yeh JTH, et al. Towards understanding cell penetration by stapled peptides. Medchemcomm. 2015;6:111–9. [DOI]

169.

Chen Z, Yu X, Zhang A, Wang F, Xing Y. De novo hydrocarbon-stapling design of single-turn α-helical antimicrobial peptides. Int J Pept Res Ther. 2019;26:1711–9. [DOI]

170.

Hirano M, Saito C, Yokoo H, Goto C, Kawano R, Misawa T, et al. Development of antimicrobial stapled peptides based on magainin 2 sequence. Molecules. 2021;26:444. [DOI] [PubMed] [PMC]

171.

Kong X, Zhang N, Shen H, Wang N, Cong W, Liu C, et al. Design, synthesis and antitumor activity of ascaphin-8 derived stapled peptides based on halogen–sulfhydryl click chemical reactions. RSC Adv. 2023;13:19862–8. [DOI] [PubMed] [PMC]

172.

You Y, Liu H, Zhu Y, Zheng H. Rational design of stapled antimicrobial peptides. Amino Acids. 2023;55:421–42. [DOI] [PubMed]

173.

Zeng Z, Zhu J, Deng X, Chen H, Jin Y, Miclet E, et al. Customized reversible stapling for selective delivery of bioactive peptides. J Am Chem Soc. 2022;144:23614–21. [DOI] [PubMed]

174.

Tran PT, Larsen CØ, Røndbjerg T, De Foresta M, Kunze MB, Marek A, et al. Diversity-oriented peptide stapling: a third generation copper-catalysed azide–alkyne cycloaddition stapling and functionalisation strategy. Chemistry. 2017;23:3490–5. [DOI] [PubMed]

175.

Pei Z, Lei H, Cheng L. Bioactive inorganic nanomaterials for cancer theranostics. Chem Soc Rev. 2023;52:2031–81. [DOI] [PubMed]

176.

Krajcovicova S, Spring DR. Tryptophan in multicomponent petasis reactions for peptide stapling and late-stage functionalisation. Angew Chem Int Ed Engl. 2023;62:e202307782. [DOI] [PubMed]

177.

Li Z, Huang R, Xu H, Chen J, Zhan Y, Zhou X, et al. Divinylsulfonamides as specific linkers for stapling disulfide bonds in peptides. Org Lett. 2017;19:4972–5. Erratum in: Org Lett. 2018;20:2127. [DOI] [PubMed]

178.

Grison CM, Burslem GM, Miles JA, Pilsl LKA, Yeo DJ, Imani Z, et al. Double quick, double click reversible peptide “stapling”. Chem Sci. 2017;8:5166–71. [DOI] [PubMed] [PMC]

179.

Kalderon D, Roberts BL, Richardson WD, Smith AE. A short amino acid sequence able to specify nuclear location. Cell. 1984;39:499–509. [DOI] [PubMed]

180.

Conti E, Kuriyan J. Crystallographic analysis of the specific yet versatile recognition of distinct nuclear localization signals by karyopherin α. Structure. 2000;8:329–38. [DOI] [PubMed]

181.

Yang Y. Structure, function and regulation of the melanocortin receptors. Eur J Pharmacol. 2011;660:125–30. [DOI] [PubMed] [PMC]

182.

Rosenkranz AA, Slastnikova TA, Durymanov MO, Sobolev AS. Malignant melanoma and melanocortin 1 receptor. Biochemistry (Mosc). 2013;78:1228–37. [DOI] [PubMed] [PMC]

183.

López MN, Pereda C, Ramírez M, Mendoza-Naranjo A, Serrano A, Ferreira A, et al. Melanocortin 1 receptor is expressed by uveal malignant melanoma and can be considered a new target for diagnosis and immunotherapy. Invest Ophthalmol Vis Sci. 2007;48:1219–27. [DOI] [PubMed]

184.

Larkin J, Ascierto PA, Dréno B, Atkinson V, Liszkay G, Maio M, et al. Combined vemurafenib and cobimetinib in BRAF-mutated melanoma. N Engl J Med. 2014;371:1867–76. [DOI] [PubMed]

185.

Gooding M, Adigbli D, Edith Chan AW, Melander RJ, MacRobert AJ, Selwood DL. A bifurcated proteoglycan binding small molecule carrier for siRNA delivery. Chem Biol Drug Des. 2014;84:24–35. [DOI] [PubMed] [PMC]

186.

Rebstock AS, Visintin C, Leo E, Garcia Posada C, Kingsbury SR, Williams GH, et al. Modular assembly using sequential palladium coupling gives easy access to the SMoC class of cellular transporters. Chembiochem. 2008;9:1787–96. [DOI] [PubMed]

187.

Okuyama M, Laman H, Kingsbury SR, Visintin C, Leo E, Eward KL, et al. Small-molecule mimics of an α-helix for efficient transport of proteins into cells. Nat Methods. 2007;4:153–9. [DOI] [PubMed]

188.

Xiao Q, Bécar NA, Brown NP, Smith MS, Stern KL, Draper SRE, et al. Stapling of two PEGylated side chains increases the conformational stability of the WW domain via an entropic effect. Org Biomol Chem. 2018;16:8933–9. [DOI] [PubMed] [PMC]

189.

Preston GW, Wilson AJ. Photo-induced covalent cross-linking for the analysis of biomolecular interactions. Chem Soc Rev. 2013;42:3289–301. [DOI] [PubMed]

190.

Saghatelian A, Jessani N, Joseph A, Humphrey M, Cravatt BF. Activity-based probes for the proteomic profiling of metalloproteases. Proc Natl Acad Sci U S A. 2004;101:10000–5. [DOI] [PubMed] [PMC]

191.

Sumranjit J, Chung SJ. Recent advances in target characterization and identification by photoaffinity probes. Molecules. 2013;18:10425–51. [DOI] [PubMed] [PMC]

192.

Braun CR, Mintseris J, Gavathiotis E, Bird GH, Gygi SP, Walensky LD. Photoreactive stapled BH3 peptides to dissect the BCL-2 family interactome. Chem Biol. 2010;17:1325–33. [DOI] [PubMed] [PMC]

193.

Wu Y, Olsen LB, Lau YH, Jensen CH, Rossmann M, Baker YR, et al. Development of a multifunctional benzophenone linker for peptide stapling and photoaffinity labelling. Chembiochem. 2016;17:689–92. [DOI] [PubMed] [PMC]

194.

Bhardwaj G, O’Connor J, Rettie S, Huang YH, Ramelot TA, Mulligan VK, et al. Accurate de novo design of membrane-traversing macrocycles. Cell. 2022;185:3520–32.E26. [DOI] [PubMed] [PMC]

195.

Tallorin L, Wang J, Kim WE, Sahu S, Kosa NM, Yang P, et al. Discovering de novo peptide substrates for enzymes using machine learning. Nat Commun. 2018;9:5253. [DOI] [PubMed] [PMC]

196.

Ma Y, Guo Z, Xia B, Zhang Y, Liu X, Yu Y, et al. Identification of antimicrobial peptides from the human gut microbiome using deep learning. Nat Biotechnol. 2022;40:921–31. [DOI] [PubMed]