Propargyl-Assisted Selective Amidation Applied in C-terminal Glycine Peptide Conjugation.


Alkyl esters, such as propargyl esters, typically lack the electron-withdrawing inductive effects needed to participate in nucleophilic acyl substitution reactions. Herein, we report an unusual observation in which glycine propargyl ester derivatives displayed selective, base-independent reactivity towards linear alkylamines under mild, metal-free conditions. Through global reaction route mapping (GRRM) modeling calculations, it is predicted that these observations may be governed by factors related to hydrogen-bonding and intermolecular interactions, rather than electron-withdrawing inductive effects. Based on this concept of propargyl-assisted selective amidation, a direct application was made to develop a novel site-specific C-terminal glycine peptide bioconjugation technique as a proof-of-concept, which relies upon the selective reactivity of glycine propargyl esters over that of aspartate and glutamate side-chain-linked propargyl esters.

DOI: 10.1002/chem.201604247

Cite this paper

@article{Vong2016PropargylAssistedSA, title={Propargyl-Assisted Selective Amidation Applied in C-terminal Glycine Peptide Conjugation.}, author={Kenward King Ho Vong and Satoshi Maeda and Katsunori Tanaka}, journal={Chemistry}, year={2016}, volume={22 52}, pages={18865-18872} }