THE AMINO-ACID-SEQUENCE CODED BY THE RARELY EXPRESSED EXON 26A OF HUMAN ELASTIN CONTAINS A STABLE BETA-TURN WITH CHEMOTACTIC ACTIVITY FOR MONOCYTES

The structural and biological properties of the amino acid sequence co ded by the rarely expressed exon 26A of human elastin were investigate d. The C-terminal portion of this sequence, corresponding to residues 600-619 of human tropoelastin, REGDPSSSQHLPSTPSSPRV and three shorter derived peptides, LREGDPSS, SSSQHLPS, and LPSTPSSP, were synthesized a nd studied. Spectroscopic analyses by CD and NMR have identified a typ e II beta-turn within the sequence REGD of the octapeptide LREGDPSS. T his structural motif was found also in the tetrapeptide REGD in both t rifluoroethanol and water. The CD spectrum of the tetrapeptide REGD in trifluoroethanol was consistent with a pure type II beta-turn. A high chemotactic activity for monocytes was exhibited by the structured pe ptides REGD (CI 0.90 at 10(-7) M) and LREGDPSS (CI 0.80 at 10(-11) M), at variance with the unfolded peptides LPSTPSSP and SSSQHLPS, suggest ing that this activity is strictly con-elated with folded structures. Because the exon 26A of human elastin is expressed in the neointima of hypertensive pulmonary arteries, and macrophages are present in this pathologic tissue [Liptay et al. (1993) J. Clin. Invest. 91, 588-594], the chemotactic activity for human monocytes reported in this paper i s consistent with an active role played by the exon 26A in inducing th e migration of the monocyte/macrophage cells to the neointima.