Biocompatible Macrocyclization between Cysteine and 2-Cyanopyridine Generates Stable Peptide Inhibitors

Christoph Nitsche*, Hideki Onagi, Jun Ping Quek, Gottfried Otting, Dahai Luo, Thomas Huber

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    44 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    Pages (from-to)4709-4712
    Number of pages4
    JournalOrganic Letters
    Volume21
    Issue number12
    DOIs
    Publication statusPublished - 21 Jun 2019

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