The influence of molecular conformation upon the self-assembly of cyclohexane diamide diacids

Background: Information regarding the self-association of small peptide motifs can be used in the design of peptide microstructures. Previous work in our laboratories illustrated the self-association of certain diamide diacids into microcapsules. In this report a series of cyclohexane diamide diacids are investigated. The cyclohexylene (R-C6H10-R) system (with its axial and equatorial requirements) provided an opportunity to study the influence of molecular conformation upon the self-aggregation process. Results: Condensation of the respective cis- and trans-1,2-, 1,3-, and 1,4-cyclohexane dicarboxylic acid platforms with two equivalents of a L-Phe ester followed by deprotection gave the desired diamide diacids. Basic solutions of cis-1,2-,trans-1,3-, and cis-1,4-diamide diacids generated solid microspheres when acidified to pH 2.4 Molecular modeling revealed that 1,3-diaxial interactions favor a helical turn within these diamides. Conclusions: Access to 'complementary' molecular geometries is needed to self-associate into microscopic architectures. (C) 1997 Elsevier Science Ltd.