Position matters in ester thiolysis by cysteine-containing peptides in micelles and vesicles

Abstract

Hypothesis: The interaction of peptides with nanoaggregates is an active research topic. Cysteine (Cys)-containing peptides open opportunities for developing low molecular weight compounds with interesting properties and potential applications. Knowledge of the relationship between the position of the Cys in the peptides and the aggregate interface is essential. Experiments: We synthesized a series of Cys-containing peptides having a variable number of glycines (Gly) as spacers between the N-palmitoyl chain at their N-terminal portion and Cys at their carboxy-terminal. The apparent pKa of the Cys-thiol group of each peptide was measured in micelles of CTAC (hexadecyltrimethylammonium chloride) and vesicles of DHDAC (dihexadecyldimethylammonium chloride). No clear correlation existed between the pKa’s and the number of Gly in the peptides. However, the rate of p-nitro-phenyl-octanoate (NPO) thiolysis by the peptides in micelles and vesicles decreased regularly with peptide length. Molecular Dynamics (MD) analysis of the peptides in CTAC micelles was carried out. Findings: pKa determinations and rate dependence of the peptides in a thiolysis reaction and MD analysis strongly suggested that the higher rates observed with shorter peptides can be attributed to an increased probability of Cys being located below the micellar surface, where the carbonyl reaction center of NPO resides.

Keywords

• Ester thiolysis
• Cysteine-containing hydrophobic peptides
• Micelles
• Vesicles
• Molecular dynamics of micelle-incorporated peptides