Illustration of the structures of designed bicyclic peptides conjugated with a vinyl sulfone warhead. The primary amino acid sequences of the designed peptides were followed by the inhibition rate at a fixed concentration of 10 μM or 1 μM. Those with potent inhibition of > 80% were further characterized for their IC50
A series
B series
Name
Amino acid sequences
Inhibition (%)
IC50 ± SD (nM)
BCP-1A
Ala-Cys-Val-Leu-Gln-Cys-Gly-Phe-Arg-Cys
50.1% at 10 μM
-
BCP-1B
Ala-Cys-Val-Leu-Gln-Cys-Gly-Phe-Arg-Cys
68.2% at 10 μM
-
BCP-2A
Ala-Cys-Ser-Gly-Phe-Arg-Cys-Arg-Val-Trp-Cys
62.8% at 10 μM
-
BCP-2B
Ala-Cys-Ser-Gly-Phe-Arg-Cys-Arg-Val-Trp-Cys
63.0% at 10 μM
-
BCP-3A
Ala-Cys-Ser-Gly-Phe-Arg-Pro-Cys-Arg-Val-Trp-Cys
62.0% at 10 μM
-
BCP-3B
Ala-Cys-Ser-Gly-Phe-Arg-Pro-Cys-Arg-Val-Trp-Cys
75.6% at 10 μM
-
BCP-4A
Ala-Cys-Ser-Gly-Phe-Arg-Cys-Arg-Pro-Val-Trp-Cys
60.5% at 10 μM
-
BCP-4B
Ala-Cys-Ser-Gly-Phe-Arg-Cys-Arg-Pro-Val-Trp-Cys
66.0% at 10 μM
-
BCP-5A
Ala-Cys-Arg-Gly-Ser-Gly-Cys-Pro-Asn-Ser-Thr-Cys
53.4% at 10 μM
-
BCP-5B
Ala-Cys-Arg-Gly-Ser-Gly-Cys-Pro-Asn-Ser-Thr-Cys
55.7% at 10 μM
-
BCP-6A
Ala-Cys-Gly-Ser-Gly-Arg-Cys-Ser-Gly-Val-Leu-Cys
53.3% at 10 μM
-
BCP-6B
Ala-Cys-Gly-Ser-Gly-Arg-Cys-Ser-Gly-Val-Leu-Cys
55.3% at 10 μM
-
BCP-7A
Ala-Cys-Ser-Gly-Thr-Arg-Cys-Ser-Gly-Phe-Leu-Cys
50.1% at 10 μM
-
BCP-7B
Ala-Cys-Ser-Gly-Thr-Arg-Cys-Ser-Gly-Phe-Leu-Cys
52.0% at 10 μM
-
BCP-8A
Ala-Cys-Ala-Gly-Arg-Cys-Pro-Ser-Ala- Cys-Leu
82.2% at 1 μM
357.43 ± 29.70 nM
BCP-8B
Ala-Cys-Ala-Gly-Arg-Cys-Pro-Ser-Ala- Cys-Leu
96.8% at 1 μM
153.63 ± 17.87 nM
BCP-8BNO
Ala-Cys-Ala-Gly-Arg-Cys-Pro-Ser-Ala- Cys-Leu
8.7% at 1 μM
-
-: no data. SD: standard deviation; TATA: 1,3,5-triacryloylhexahydro-1,3,5-triazine; TBMB: 1,3,5-tris(bromomethyl)benzene; BCP: bicyclic peptide; IC50: half-maximal inhibitory concentration
We acknowledge the instrument facility of the Biotech Drug Research Center for providing support with mass spectrometry, protein expression, and plate reader. We also acknowledge the institutional center for Shared Technologies and Facilities of SIMM for providing services including NMR and MS data recording.
Author contributions
QW: Conceptualization, Validation, Formal analysis, Investigation, Data curation, Writing—original draft. YW and JL: Conceptualization, Data curation, Supervision. HL and SC: Conceptualization, Resources, Supervision, Writing—original draft, Writing—review & editing, Project administration, Funding acquisition, Resources. 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
The raw data supporting the conclusions of this manuscript will be made available by the corresponding author, without undue restriction, to any qualified researcher upon request.
Funding
This study was supported by the Distinguished Young Scholars Program and the General Program of the National Natural Science Foundation of China (#22477128) awarded to SC. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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A series
B series