Biocompatible macrocyclization between cysteine and 2-cyanopyridine generates stable peptide inhibitors

Biocompatible macrocyclization between cysteine and 2-cyanopyridine generates stable peptide inhibitors

Peptides featuring an N-terminal cysteine residue and the unnatural amino acid 3-(2-cyano-4-pyridyl)alanine (Cpa) cyclize spontaneously in aqueous solution at neutral pH. Cpa is readily available and easily introduced into peptides using standard solid-phase peptide synthesis. The reaction is orthog...

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Bibliographic Details
Main Authors: Nitsche, Christoph, Onagi, Hideki, Quek, Jun-Ping, Otting, Gottfried, Luo, Dahai, Huber, Thomas
Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
Format: Article
Language:English
Published: 2020
Subjects:
Science::Medicine
Peptides and Proteins
Monomers
Online Access:https://hdl.handle.net/10356/140796
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Institution: Nanyang Technological University
Language: English
Description
Summary:Peptides featuring an N-terminal cysteine residue and the unnatural amino acid 3-(2-cyano-4-pyridyl)alanine (Cpa) cyclize spontaneously in aqueous solution at neutral pH. Cpa is readily available and easily introduced into peptides using standard solid-phase peptide synthesis. The reaction is orthogonal to all proteinogenic amino acids, including cysteine residues that are not at the N-terminus. A substrate peptide of the Zika virus NS2B-NS3 protease cyclized in this way produced an inhibitor of high affinity and proteolytic stability.

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