Thomas F. Mitts

Classical Synthesis of and Structural Studies on a Biologically Active Heptapeptide and a Nonapeptide of Bovine Elastin

The synthesis of two elastin sequences incorporating the structural unit X-G-G-X-G (X = A) is described. In particular, the following peptides and polypeptides were synthesized and characterized: TFA−H2+LGAGGAG-OH, TFA−H2+LGAGGAGVL-OH (both of these inducing stimulation of endogenous elastin production in cultured adult human fibroblast), poly(LGAGGAG), and poly(LGAGGAGVL). The synthesis was accomplished in solution by classical procedures, by using the diphenylphosphoryl azide for the polycondensation step, and the mixed anhydride method for the coupling steps. CD, NMR, and FT-IR measurements gave evidence of quasi-extended (PP II) structures as a peculiar structural feature in the heptapeptide, and a tendency towards flexible β-turns in the nonapeptide. Poly(LGAGGAG) showed greater disorder with respect to the “monomer”, the molecular conformation being accountable for by unstructured polypeptide chains together with β-turns. The polymer is able to adopt supramolecular structures reminiscent of those found in elastin. Unlike that of the heptapeptide, polycondensation of the nonapeptide did not afford a linear polymer, but only cyclic derivatives. This could well be due to the tendency of the monomeric nonapeptide to adopt folded conformations.