COMPARISON OF THE STRUCTURES OF THE ENDOTHELIN-A RECEPTOR ANTAGONISTSBQ123 AND N-METHYL LEUCINE BQ123 WITH THE CRYSTAL-STRUCTURE OF THE C-TERMINAL TAIL OF ENDOTHELIN-1

The functionally important regions of the cyclic pentapeptide endothel in A receptor antagonist BQ123 are shown to correlate with the structu re of the C-terminal tail of endothelin-1, as found in the recently-de termined X-ray crystal structure. Residues 18 and 21 of endothelin-1 a re spatially juxtaposed such that they superpose extremely well with D -Asp and D-Trp of the antagonist, consistent with the residues on this surface of the endothelin helix being important for binding, This stu dy provides new information on the three-dimensional nature of the end othelin A receptor binding site which may prove useful for rational dr ug design.