Convergent synthesis of aminomethylene peptidomimetics

Abstract

This protocol describes a convergent synthesis of reduced amide bond peptidomimetics using thioacid-terminated peptides and aziridine-containing peptide conjugates. This approach could be used to produce peptides and proteins with modified backbones. The peptide conjugates are made using readily available aziridine aldehydes. The convergent synthesis of peptidomimetics is demonstrated through the preparation of long and short peptide fragments with an aminomethylene group incorporated within them. This transformation is amenable to the synthesis of peptides with reduced amide bonds at cysteine and alanine. The procedure describes the preparation of each component used and highlights the ease of synthesis of aminomethylene peptidomimetics, and takes about 3 d to complete.

Solution-phase-peptide synthesis via the group-assisted purification (GAP) chemistry without using chromatography and recrystallization

“…Peptides and peptidomimetic drugs are involved in nearly all disciplines of chemical and biomedical sciences. [1][2][3][4][5] The search for environmentally friendly synthetic approaches to these products for academic research and pharmaceutical production has been pursued for over five decades. [6][7][8][9][10][11] A notable accomplishment in peptide synthesis is shown by the solid-phase-peptide synthesis (SPPS) invented by the late Nobel Laureate, Bruce Merrifield, in the 1980's.…”