Endothelin peptide family structure

Fig. 8. (a) Primary structure of the cyclic endothelin antagonist BE18257B and (b) a family of 36 NMR structures which demonstrates the well-defined nature of the cyclic peptide backbone. (Reprinted with permission from Coles et a/.148 Copyright (1993) American Chemical Society.)... 

Endothehns constitute a family of peptides (Hart and Hart, 1992). They are very potent endogenous vasoconstrictors and vasopressors and are secreted by various cells and tissues in the human body. Of the three isoforms, endothe-hn-1 (ET-1) is one of the most potent contractors of vascular smooth muscles (Miller et al, 1993). Endothelins have very similar structures and biological properties to sarafotoxins (Kloog and Sokolovsky, 1989), and the toxic peptides are obtained from the venom of mole vipers (Atractaspidae). 

The endothelins belong to a family of potent vasoconstrictor peptides that were originally isolated from the supernatant of cultured aortic endothelial cells. Endothehns bear striking structural similarities to the sarafotoxins, which are potent cardiotoxic peptides isolated from the venom of the burrowing asp Atractaspis engadensis. Four endothelins and four sarafotoxin isopeptides, having different receptor sub-types, have been identified (see also Figure 44). 

Sarafotoxins (SRTX), CSCKDMTDKE CL NFCHQDVTIw (SRTX-a) (disulfide bonds C -C /C -C ), a family of vasoactive peptides initially isolated from the venom of Atractaspis engaddensis. The highly toxic peptides (SRTX-a, -h, -c, -e) are structurally and functionally related to endothelins (ET). Each of the members of the ET-SRTX family contains four Cys, and about 60-70% of their 21 amino acid residues are identical. The SRTX cause strong vasoconstriction of coronary arteries. Death after intoxication with SRTX peptides is the result of cardiac ischemia or infarction. Sarafotoxins and sarafotoxin-like peptides are produced by various snake... 

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