Contemporary Approaches to α,β-Dehydroamino Acid Chemical Modifications

Abstract

As one of the most common unnatural amino acids(uAAs), α,β-dehydroamino acids(α,β-dhAAs) can be found in various ribosomally synthesized and post-translationally modified peptides(RiPPs) and other naturally occurring peptides. In recent years, novel reactions for α,β-dhAA modification continue to emerge. Due to their unique electrophilicity different from 20 natural amino acids, α,β-dhAAs, especially dehydroalanine(Dha), have become powerful tools for site-selective protein modification. In this review, we mainly focus on the latest research progress of C—C and C-heteroatom(C—X, X=S, N, Se, Si, P, B) bond formation methods based on α,β-dhAAs in the past five years. Particularly, we pay much attention to the α,β-dhAA derivatization methodologies used in the late-stage modification for natural peptides and proteins. In addition, we also focus on the downstream functionalization and therapeutic biologic applications of these modifications.

Keywords

Dehydroamino acid / Peptide / Protein / Chemical modification

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