STRUCTURE-ACTIVITY STUDY OF THE C-TERMINAL RESIDUE OF MEN-10207 TACHYKININ ANTAGONIST

The role of the C-terminal residue in the sequence of the NK-2- selective tachykinin antagonist, MEN 10207 (Asp-Tyr-D-Trp-Val-D-Trp-D-Trp-Arg-NH2). has been examined by systematic amino acid substitutions. Biological activity has been measured on two in vitro preparations chosen as paradigms of the recently described NK-2 receptor subtypes, namely the rabbit pulmonary artery and the hamster trachea, in order to define the structural requirements necessary for antagonist subtype selectivity. We conclude that in the presence of a C-terminal hydrophilic residue, affinity is maximal for the NK-2A subtype. while hydrophobic. bulky and aromatic residues increase affinity for the NK-2B subtype.