Residue-Specific Peptide Modification: A Chemist’s Guide

Abstract

Advances in bioconjugation and native protein modification are appearing at a blistering pace, making it increasingly time consuming for practitioners to identify the best chemical method for modifying a specific amino acid residue in a complex setting. The purpose of this perspective is to provide an informative, graphically rich manual highlighting significant advances in the field over the past decade. This guide will help triage candidate methods for peptide alteration and will serve as a starting point for those seeking to solve long-standing challenges.

Arylation Chemistry for Bioconjugation

“…Throughout this review,w ee mphasize the fundamental chemistry of arylative bioconjugation reactions.The complex nature of bioconjugates requires well-designed reagents and conditions as well as accurate product characterization prior to employing the resulting conjugates for biological applications.W eb elieve that there is no perfect bioconjugation reaction that fulfills all application needs.This review aims to complement other recent reviews on bioconjugation [42][43][44][45][46][47][48][49][50][51][52][53][54] and provide the reader with an expanded understanding of current bioconjugation techniques. We then describe the N-arylation of the e-amine of lysine.A rylation of other natural and unnatural amino acid side chains is also discussed with afocus on the umpolung arylation of selenocysteine and the palladium-catalyzed cross-coupling reactions for protein modification.…”

Site- and Stereoselective Chemical Editing of Thiostrepton by Rh-Catalyzed Conjugate Arylation: New Analogues and Collateral Enantioselective Synthesis of Amino Acids

“…14 Unlike the canonical twenty amino acids, dehydroalanine is electrophilic, making it suitable for selective functionalization even within the complex environment of a natural product, peptide, or protein. 15,16 As such, a strategy for catalytic, nucleophilic addition to dehydroalanines in a complex environment would enable post-synthetic, catalyst-controlled chemical editing of many naturally-occurring compounds (Fig. 1).…”

Arylierungschemie für die Biokonjugation

“…Dieser Aufsatz verfolgt das Ziel, die Sichtweise anderer kürzlich erschienener Zusammenfassungen von Biokonjugationsmethoden [42][43][44][45][46][47][48][49][50][51][52][53][54] zu ergänzen und dem Leser ein breiteres Verständnis gegenwärtiger Biokonjugationstechniken zu vermitteln. Die vielgestaltige Beschaffenheit solche Biokonjugate bedarf maßgeschneiderter Reagentien und Bedingungen sowie genauer Charakterisierung der Produkte,b evor diese fürbiologische Anwendungen eingesetzt werden kçnnen.…”