Hunt J T, Lee V G, McMullen D, Liu E C, Bolgar M, Delaney C L, Festin S M, Floyd D M, Hedberg A, Natarajan S
Department of Chemistry, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543-4000.
Bioorg Med Chem. 1993 Jul;1(1):59-65. doi: 10.1016/s0968-0896(00)82103-3.
With the goal of producing receptor antagonists, numerous monocyclic and bicyclic endothelin analogs were prepared and tested for vasoconstrictor activity, receptor affinity and functional antagonist activity. Bis-penicillamine endothelin analogs containing Ala or Asn at position 18 were functional antagonists, with Ki values of 20-40 nM but KB values of about 1 microM (e.g., [Pen1,11, Nle7, Ala18]-endothelin-1, Ki = 42 nM, KB = 1.2 microM). While these peptides are antagonists at the ETA receptor, they appear to be at least partial agonists at another receptor subtype.
