Spontaneous Intermolecular Amide Bond Formation between Side Chains for Irreversible Peptide Targeting

摘要

Peptides and synthetic peptide-like molecules are powerful toolsnfor analysis and control of biological function.1-3 One majornproblem with the use of peptides is the instability of theirninteractions with biomolecules, with typically micromolar affinitynrelating to the limited accessible surface area4,5 and the intrinsicnflexibility of peptides.6 However, appending a short peptide tag isnthe most common way to allow a protein of interest to be isolatednor detected, giving minimum perturbation to protein function.7,8nHere we have designed a way to bind a peptide tag irreversibly,nby adapting a recently discovered feature of amino acid chemistry:nthe spontaneous formation of an amide bond between a Lys andnan Asn side chain in the appropriate environment.9-11