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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Biocompatible Materials / chemical synthesis
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Biocompatible Materials / chemistry
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Biocompatible Materials / pharmacology*
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Cyclization
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Cysteine / chemistry
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Cysteine / pharmacology*
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Molecular Structure
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Peptides / antagonists & inhibitors*
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Pyrimidines / chemistry
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Pyrimidines / pharmacology*
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RNA Helicases / chemistry
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Serine Endopeptidases / chemistry
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Viral Nonstructural Proteins / chemistry
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Zika Virus / enzymology
Substances
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Biocompatible Materials
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NS2B protein, flavivirus
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NS3 protein, flavivirus
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Peptides
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Pyrimidines
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Viral Nonstructural Proteins
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Serine Endopeptidases
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RNA Helicases
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Cysteine