SYNTHESIS AND CHARACTERIZATION OF THE HUMAN ELASTIN W4 SEQUENCE

Following the nomenclature of Sandberg, the W4 sequence of human elast in, LVPGGPGFGPGVVGVP- GAGVPGVGVPGAGIPVVPGAGIPGAGVPGVVSPEG, has been sy nthesized by solid-phase methods and characterized by carbon-13 nuclea r magnetic resonance, amino-acid analysis, mass spectra and elemental analysis. This sequence was then polymerized to greater than 50 kDa as determined by retention in 50 kDa molecular weight cut-off dialysis t ubing. It has been successfully cross-linked by gamma-irradiation (20 Mrad) to form an elastomeric matrix, designated as X(20)-poly(W4). Phy sical characterizations such as stress/strain, thermoelasticity, acid- base titration and inverse temperature transition studies have been ca rried out on this elastomer, which is homologous to the striking, poly (VPGVG), W4 sequence of bovine and porcine elastins. These results are compared with previous results on the polypentapeptide of elastin, (V PGVG),, and it has been demonstrated that X(20)-poly(W4) also is a dom inantly entropic elastomer. Finally, the working model for the structu re of this human elastin sequence was derived computationally using mo lecular mechanics and dynamics calculations. Thus the human W4 sequenc e appears to be structurally and functionally equivalent to the bovine and porcine W4 sequences in spite of the less regular repeating penta mer sequence. (C) Munksgaard 1995.