Synthesis of polypeptide models of collagen

It is well known that the amino acid sequence of collagen contains a large number of tripeptide units such as Y-X-Gly, where Y and X can be any amino acid residue but most frequently are proline or hydroxyproline. Accordingly, several sequential polytripeptides, including repeating sequences of that type containing one or two imino acid residues, have been synthesized and studied in solution and/or in the solid state (1–14). In this paper we describe in detail the syntheses via active esters of four polytripeptides of the type poly(Pro-X-Gly) and poly(X-Pro-Gly), where X is isoleucine or norleucine. The general objective was to study the influence of hydrophobic residues on the stability of collagen three-dimensional structure; in particular we were interested in the introduction of branching at C^β in view of the recent calculations of Némethy & Scheraga (15). The Nle residue was introduced in order to obtain reference polymers without any branching in the side chain. By way of comparison, we have shown earlier that polymeric sequences where X is leucine (branching at the C^γ) possess collagen-like structures in an appropriate milieu (10, 11). The results of both theoretical and experimental conformational studies on the polymers will be published in a forthcoming paper. Syntheses via p-nitrophenyl esters are described for poly(Pro-Ile-Gly), poly(Ile-Pro-Gly), poly(Pro-Nle-Gly) and poly(Nle-Pro-Gly), four synthetic polytripeptide analogues of the non-polar regions of collagens. The obtained polymers exhibit molecular weights in the range 5000–10000 as judged from viscosity measurements.