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Michael Addition Reaction between Dehydroalanines and Phosphites Enabled the Introduction of Phosphonates into Oligopeptides

Changjun Yu, E Ruiyao, Yingying An, Xiaomin Guo, Guangjun Bao, Yiping Li, Junqiu Xie, Wangsheng Sun

2024Organic Letters13 citationsDOI

Abstract

A method for introducing a range of phosphonates into oligopeptides through a Michael addition reaction between dehydroalanine and phosphite is presented. The method offers a mild, cheap, and straightforward approach to peptide phosphorylation that has potential applications in chemical biology and medicinal chemistry. Moreover, the introduction of a phosphonate group into short antibacterial peptides is described to demonstrate its utility, leading to the discovery of phosphonated antibacterial peptides with potent broad-spectrum antibacterial activity.

Topics & Concepts

ChemistryDehydroalaninePhosphonateOligopeptideCombinatorial chemistryAntibacterial peptidePeptideAntimicrobialStereochemistryOrganic chemistryAntibacterial activityBiochemistryBacteriaBiologyGeneticsChemical Synthesis and AnalysisClick Chemistry and ApplicationsRNA and protein synthesis mechanisms
Michael Addition Reaction between Dehydroalanines and Phosphites Enabled the Introduction of Phosphonates into Oligopeptides | Litcius