Stereochemical Dependence of the Self-Assembly of the Immunoadjuvants Pam3Cys and Pam3Cys-Ser

The lipopeptide tripalmitoyl- S -glycerylcysteine (Pam 3 Cys) is derived from the N -terminal part of bacterial lipopeptides and is a polyclonal B-lymphocyte and macrophage activator. Derivatives of Pam 3 Cys constitute highly potent, nontoxic immunoadjuvants, and lipopeptide−antigen conjugates have found important applications as novel fully synthetic low-molecular-weight vaccines. To establish a possible correlation between molecular structure, aggregation properties, and biological activities, we have studied the self-assembly and monolayer properties of a range of Pam 3 Cys derivatives using transmission electron microscopy (TEM) and a Langmuir-film balance combined with a Brewster angle microscopy (BAM). It was found that the chirality of the glyceryl moiety and the additional serine unit impacted on the mode of aggregation and the monolayer properties. Correlations are discussed between these physicochemical properties and biological activities.