Table Info

Table 2.

Scope of the C-terminal amino acids in conversion to carboxylic acids

Entry	Xaa	Product	HPLC purity of 2 (%)^a
Entry	Xaa	Product	Oxone	BME
1	Gly	2a	84	82
2	Ala	2b	82	82
3	Val	2c	77	76
4	Ile	2d	63	61 (74)^b
5	Leu	2e	80	79
6	Phe	2f	87	89
7	Pro	2g	77	65 (87)^b
8	Ser	2h	82	81
9	Thr	2i	81	91
10	Glu	2j	81	95
11	Cys	2k	< 1	66
12	Cys(Acm)	2k’	< 1	-
13	Met	2l	< 1	80
14	Tyr	2m	81	87
15	His	2n	81	85
16	Lys	2o	76	75
17	Arg	2p	84	60
18	Trp	2q	< 1	86

^a detected at 220 nm; ^b after the addition of BME, a 20 h reaction was performed. -: not examined

Supplementary materials

The supplementary material for this article is available at: https://www.explorationpub.com/uploads/Article/file/100823_sup_1.pdf.

Declarations

Acknowledgments

ST is grateful for a scholarship from the Amano Institute of Technology.

Author contributions

ST: Investigation, Writing—original draft. MK: Investigation. YT: Methodology. TN and NM: Writing—review & editing, Supervision. KS: Conceptualization, Funding acquisition, Writing—original draft, Writing—review & editing. All authors read and approved the submitted version.

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

This research was supported in part by JSPS KAKENHI Grant number [JP22K05349] and Research Institute of Green Science and Technology Fund for Research Project Support [2023-RIGST-22201] National University Corporation Shizuoka University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Copyright

References

Wang L, Wang N, Zhang W, Cheng X, Yan Z, Shao G, et al. Therapeutic peptides: current applications and future directions. Sig Transduct Target Ther. 2022;7:48. [DOI] [PubMed] [PMC]

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

Arbour CA, Mendoza LG, Stockdill JL. Recent advances in the synthesis of C-terminally modified peptides. Org Biomol Chem. 2020;18:7253–72. [DOI] [PubMed] [PMC]

Alsina J, Albericio F. Solid-phase synthesis of C-terminal modified peptides. Pept Sci. 2003;71:454–77. [DOI] [PubMed]

Moss JA. Guide for resin and linker selection in solid-phase peptide synthesis. Curr Protoc Protein Sci. 2005;40:18.7.1–19. [DOI] [PubMed]

Sato K, Tanaka S, Wang J, Ishikawa K, Tsuda S, Narumi T, et al. Late-stage solubilization of poorly soluble peptides using hydrazide chemistry. Org Lett. 2021;23:1653–8. [DOI] [PubMed]

Fabre B, Pícha J, Vaněk V, Buděšínský M, Jiráček J. A CuAAC–hydrazone–CuAAC trifunctional scaffold for the solid-phase synthesis of trimodal compounds: possibilities and limitations. Molecules. 2015;20:19310–29. [DOI] [PubMed] [PMC]

Srinivas R, Reddy BVS, Yadav JS, Ramalingam T. An efficient and selective conversion of hydrazides into esters and acids. J Chem Res. 2000;2000:376–7. [DOI]

Takale BS, Telvekar VN. Selective oxidation of hydrazides using o-iodoxybenzoic acid to carboxylic acids, esters, and aldehydes. Chem Lett. 2010;39:546–7. [DOI]

10.

Cheung HT, Blout ER. The hydrazide as a carboxylic-protecting group in peptide synthesis. J Org Chem. 1965;30:315–6. [DOI] [PubMed]

11.

Gates ZP, Stephan JR, Lee DJ, Kent SBH. Rapid formal hydrolysis of peptide-^αthioesters. Chem Commun. 2013;49:786–8. [DOI] [PubMed]

12.

Zuo C, Yan BJ, Zhu HY, Shi WW, Xi TK, Shi J, et al. Robust synthesis of C-terminal cysteine-containing peptide acids through a peptide hydrazide-based strategy. Org Biomol Chem. 2019;17:5698–702. [DOI] [PubMed]

13.

Liang LJ, Chu GC, Qu Q, Zuo C, Mao J, Zheng Q, et al. Chemical synthesis of activity-based E2-ubiquitin probes for the structural analysis of E3 ligase-catalyzed transthiolation. Angew Chem Int Ed. 2021;60:17171–7. [DOI] [PubMed]

14.

Tsuda S, Masuda S, Yoshiya T. Solubilizing trityl-type tag to synthesize Asx/Glx-containing peptides. Chembiochem. 2019;20:2063–9. [DOI] [PubMed]

15.

Staudinger H, Meyer J. Über neue organische phosphorverbindungen III. Phosphinmethylenderivate und phosphinimine. Helv Chim Acta. 1919;2:635–46. German. [DOI]

16.

Bessalle R, Gorea A, Shalit I, Metzger JW, Dass C, Desiderio DM, et al. Structure-function studies of amphiphilic antibacterial peptides. J Med Chem. 1993;36:1203–9. [DOI] [PubMed]

17.

Huang YC, Chen CC, Li SJ, Gao S, Shi J, Li YM. Facile synthesis of C-terminal peptide hydrazide and thioester of NY-ESO-1 (A39-A68) from an Fmoc-hydrazine 2-chlorotrityl chloride resin. Tetrahedron. 2014;70:2951–5. [DOI]

18.

Eissler S, Kley M, Bächle D, Loidl G, Meier T, Samson D. Substitution determination of Fmoc-substituted resins at different wavelengths. J Pept Sci. 2017;23:757–62. [DOI] [PubMed] [PMC]

19.

Fang GM, Li YM, Shen F, Huang YC, Li JB, Lin Y, et al. Protein chemical synthesis by ligation of peptide hydrazides. Angew Chem Int Ed. 2011;50:7645–9. [DOI] [PubMed]

20.

Sato K, Tanaka S, Yamamoto K, Tashiro Y, Narumi T, Mase N. Direct synthesis of N-terminal thiazolidine-containing peptide thioesters from peptide hydrazides. Chem Commun. 2018;54:9127–30. [DOI] [PubMed]

21.

Hayashi K, Morooka N, Yamamoto Y, Fujita K, Isono K, Choi S, et al. Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110. Mol Syst Biol. 2006;2:2006.0007. [DOI] [PubMed] [PMC]

22.

Kulkarni PP, Kadam AJ, Desai UV, Mane RB, Wadgaonkar PP. A simple and efficient oxidation of hydrazides to N,N’-diacylhydrazines using Oxone® in an aqueous medium. J Chem Res. 2000;2000:184–5. [DOI]

23.

Dennison SR, Phoenix DA. Influence of C-terminal amidation on the efficacy of modelin-5. Biochemistry. 2011;50:1514–23. [DOI] [PubMed]

24.

Li W, Tailhades J, Hossain MA, O’Brien-Simpson NM, Reynolds EC, Otvos L, et al. C-Terminal modifications broaden activity of the proline-rich antimicrobial peptide, Chex1-Arg20. Aust J Chem. 2015;68:1373–8. [DOI]

25.

Dennison SR, Hauß T, Badiani K, Harris F, Phoenix DA. Biophysical investigation into the antibacterial action of modelin-5-NH₂. Soft Matter. 2019;15:4215–26. [DOI]