Chemoselective acylation of fully deprotected hydrazino acetyl peptides. Application to the synthesis of lipopetides.
Fully deprotected N-terminal alpha-hydrazino acetyl peptides were synthesized and chemoselectively acylated on the hydrazine moiety with various fatty acid succinimidyl esters or N-(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 pKa of the alpha-hydrazino acetyl group on our model peptide was found to be 6.45, i.e., about 2 units lower than the pKa of a glycyl residue. The reaction was subsequently applied to the synthesis of a 38AA peptide derivatized by a palmitoyl group.
Bonnet
D
D
UMR 8525 CNRS-Institut Pasteur de Lille-Université de Lille 2, Institut de Biologie de Lille, 1 rue du Professeur Calmette 59019 Lille, France.
Ollivier
N
N
Gras-Masse
H
H
Melnyk
O
O
D000215:Acylation; D000595:Amino Acid Sequence; D004952:Esters; D005227:Fatty Acids; D006834:Hydrazines / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007202:Indicators and Reagents; D007700:Kinetics; D008074:Lipoproteins / Q000138:chemical synthesis* / Q000737:chemistry; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013388:Succinimides
D004952:Esters; D005227:Fatty Acids; D006834:Hydrazines; D007202:Indicators and Reagents; D008074:Lipoproteins; D009842:Oligopeptides; D013388:Succinimides