10.1021/jo0010577.s001 Dominique Bonnet Dominique Bonnet Nathalie Ollivier Nathalie Ollivier Hélène Gras-Masse Hélène Gras-Masse Oleg Melnyk Oleg Melnyk Chemoselective Acylation of Fully Deprotected Hydrazino Acetyl Peptides. Application to the Synthesis of Lipopeptides American Chemical Society 2000 acid succinimidyl esters hydrazino pH p K peptide acetyl hydrazine moiety Deprotected Hydrazino Acetyl Peptides 2000-12-22 00:00:00 Journal contribution https://acs.figshare.com/articles/journal_contribution/Chemoselective_Acylation_of_Fully_Deprotected_Hydrazino_Acetyl_Peptides_Application_to_the_Synthesis_of_Lipopeptides/3686604 Fully deprotected N-terminal α-hydrazino acetyl peptides were synthesized and chemoselectively acylated on the hydrazine moiety with various fatty acid succinimidyl esters or <i>N</i>-(cholesterylcarbonyloxy) succinimide to give lipopeptides of high purity. The buffer and pH were adjusted in order to minimize the oxidation of the hydrazine moiety and to achieve the best conversion and selectivity. The acylation was performed in a citrate−phosphate buffer/2-methylpropan-2-ol mixture of pH 5.1. The p<i>K</i><sub>a</sub> of the α-hydrazino acetyl group on our model peptide was found to be 6.45, i.e., about 2 units lower than the p<i>K</i><sub>a</sub> of a glycyl residue. The reaction was subsequently applied to the synthesis of a 38AA peptide derivatized by a palmitoyl group.