開催日: 2017/09/20 - 2017/09/22
Under metal-free conditions, propargyl esters are stable functional groups that typically lack the electron-withdrawing inductive effects needed to participate in nucleophilic acyl substitution reactions. Herein we report an unusual observation where glycine propargyl ester derivatives were found to selectively form amide bonds with a series of linear alkylamines under mild, aqueous conditions in a base-independent manner. Through global reaction route mapping (GRRM) modeling calculations, it is speculated that reactivity may be primarily driven via hydrogen-bonding and intermolecular interactions, rather than base catalysis. As a proof-of-concept, a site-specific C-terminal glycine peptide bioconjugation technique was designed and developed. The design of this approach relies on the selective reactivity of C-terminal glycine propargyl esters over that of aspartate and glutamate side chain-linked propargyl esters. Several small, unprotected peptides were successfully conjugated, which shows the potential for adaptation towards protein/peptide bioconjugation. In another application, glycine propargyl ester probes were investigated for their ability to selectively react with polyamines over other biological amines (ex/ amino acids/proteins and monoamine neurotransmitters). Due to higher intracellular concentrations of polyamines within rapidly-growing cancer cells, in some cases by as much as twofold compared to nomal tissues, this work could provide the potential framework in cancer targeting therapeutic applications. Kinetic and cell-based experiments shown in this presentation hope to highlight the viability of htis approach.