Sodium dodecyl sulfate significantly alters the substrate properties of insoluble elastin resulting in a severalfold stimulation of the rate at which this structural protein is hydrolyzed by pancreatic elastase ( . M. Kagan, G. D. Crombie, R. E. Jordan, W. Lewis, and C. Franzblau (1972), Biochemistry 11, 3412). The present report describes the hydrophobic and ionic properties of synthetic and naturally occurring ligands which induce similar changes in the susceptibility of elastin to proteolytic attack. Distinct chain-length requirements are in evidence for alkyl sulfate mediated effects with a minimum chain length of eight carbons necessary for sodium dodecyl sulfate-like rate enhancement. A similar minimum hydrophobic requirement is also observed for the induction of circular dichroic (CD) spectral changes in soluble -elastin by these same compounds. This correlation between enhanced elastolytic activity and the induction of CD spectral changes points to a mechanism of stimulation involving ligand-induced conformational changes in elastin polypeptide chains. In addition to a minimum hydrophobic content, however, there is a clear requirement for an anionic polar group since neutral and nonionic detergents are without effect on the rate of elastin digestion while cationic agents are strongly inhibitory. These re-XA^have previously reported that the rate of digestion of insoluble elastin by pancreatic elastase can be enhanced by as much as sixfold by the detergent, sodium dodecyl sulfate. It was shown, moreover, that this stimulation results from the formation of an elastin-detergent complex with markedly altered properties as a substrate for elastolysis (Kagan et al., 1972).These results point toward the potential of elastin ligands to serve as cosubstrates for elastolytic enzymes by positively or negatively influencing the susceptibility of elastin toward enzymatic degradation. This consideration seems all the more important in view of the essential role played by this structural protein in tissues such as blood vessels, ligament, and lung and in view of the avidity of elastic fibers for hydrophobic ligands in vivo (Kramsch et al., 1971). Indeed, elastolytic mechanisms have been implicated in cardiovascular disease (Loeven, 1969) and in emphysema (Galdston et al., 1973). We have explored, therefore, the ability of a variety of elastin ligands to influence the proteolytic attack of this protein by pancreatic elastase in vitro. The present results describe hydrophobic and ionic propt From the

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