Structure-activity studies on endothelin (16-21), the C-terminal hexapeptide of the endothelins, in the guinea-pig bronchus

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Abstract
1 We describe the results of a structure-activity study in which the C-terminal hexapeptide of the endothelins, endothelin (16–21), is compared with shorter fragments; hexapeptides bearing amino-acid substitutions and the corresponding C-terminal fragments of sarafotoxins. The guinea-pig bronchus was used in this study since it is the most sensitive preparation for endothelin (16–21) thus far developed. 2 The biological results obtained with endothelin (16–21) and analogues demonstrate that the contractile activity of the C-terminal hexapeptide of endothelin on the guinea-pig bronchus depends on quite close structural requirements, strongly suggestive of a receptor interaction. The following features appear to be essential for the biological activity: (a) the C-terminal free carboxylic function; (b) the L-configuration of Trp-21; (c) the β-carboxylic function of Asp-18; (d) the presence of Leu-17 and (e) the imidazole moiety of His-16. 3 The hexapeptide corresponding to the C-terminal portion of sarafotoxin, sarafotoxin (16–21), was devoid of biological activity. This behaviour might be related to the proposed existence of more than one receptor for the endothelin/sarafotoxin family in the guinea-pig bronchus.