Synthesis and structural studies of two collagen analogues: Poly ( l-prolyl- l-seryl-glycyl) and poly ( l-prolyl- l-alanyl-glycyl)

Abstract

Poly ( l-prolyl- l-seryl-glycyl) and poly ( l-prolyl- l-alanyl-glycyl), two synthetic polytripeptide analogues of the non-polar regions of collagen, were synthesized by polymerization of the tripeptide p-nitrophenyl esters with C -terminal glycine residues. Circular dichroism studies of the polymers indicated the presence of an ordered collagen-like structure for each polymer in solution. This ordered structure was shown to be solvent-dependent and also dependent on the molecular weight and concentration of the polymer in solution. Both polytripeptides were investigated in a variety of solvents ranging in relative hydrogen-bonding strengths from 1,3-propanediol to hexafluoroisopropanol, and an increase in the amount of ordered structure with decreasing hydrogen-bonding strength of the solvent was observed. In 1,3-propanediol, the solvent system in which the polymers exhibited the most ordered structure at room temperature, both polymers exhibited circular dichroism spectra with identical positions of the maxima and minima and similar rotatory strengths to those observed for guinea pig skin collagen. The slow attainment of stable circular dichroism spectra of heated solutions, coupled with the demonstrated concentration dependence of the spectra, shows that aggregation of the polymers takes place in solution. Molecular weight studies of both polytripeptides in their single-chain random conformation versus the presumed triple-helical associated form showed the expected threefold association of the peptide chains in solution. The threefold change in molecular weight, coupled with the similarity between the circular dichroism spectra of the polytripeptides and collagen, suggests that the observed optical properties arise from the collagen-like triple-helical structure found for both polymers in the solid state.