Investigating the Secondary Structure of Oligomeric Poly(amino acid)s

Poly(amino acid)s have garnered significant interest as biomedical materials. They consist of naturally occurring L-amino acids, which are linked via peptide bonds, both factors contribute to the inherent biocompatibility of this material. Furthermore, due to their isotacticity these polymers readily undergo self-assembly, which is exploited for the formation of drug and gene delivery vehicles and tissue engineering scaffolds and gels. However, this strong propensity for self-assembly also interferes with the polymerization process (ring-opening polymerization of amino acid N-carboxyanhydrides), as nascent chains adopt preferably a beta-sheet conformation whose rigidity impedes chain growth and leads to early chain termination. This work investigates the tendencies of gamma-benzyl L-glutamate, NE-trifluoroacetyl-L-lysine and S- carboxybenzyl-L-cysteine to form beta-sheets in the beginning of a polymerization. The results of detailed FTIR investigations of the amide I and II bands support qualitatively the quantitative results obtained by circular dichroism spectroscopy. Poly(bz-L-Glu) and p(TFA-L-Lys) form a-helices when the oligomer length reaches 10 repeat units thus, readily sustaining the living character of the polymerization. Poly(Cbz- L-Cys) oligomers have the strongest tendency to form beta-sheets, however, the addition of hydrogen-bond breaking urea to the reaction mixture diminishes beta-sheet formation and forces the growing chains into unstructured conformations.