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.
Rovero
P
P
Chemistry and Pharmacology Departments, A. Menarini Pharmaceuticals, Firenze, Italy.
Quartara
L
L
Astolfi
M
M
Patacchini
R
R
Giachetti
A
A
Maggi
C A
CA
D000595:Amino Acid Sequence; D000818:Animals; D006224:Cricetinae; D008297:Male; D008647:Mesocricetus; D008969:Molecular Sequence Data; D009119:Muscle Contraction / Q000187:drug effects*; D015288:Neurokinin A / Q000031:analogs & derivatives* / Q000494:pharmacology; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000502:physiology; D011817:Rabbits; D013329:Structure-Activity Relationship; D015320:Tachykinins / Q000037:antagonists & inhibitors*; D014132:Trachea / Q000502:physiology
D010446:Peptide Fragments; D015320:Tachykinins; C063615:neurokinin A (4-10), Tyr(5)-Trp(6,8,9)-Arg(10)-; D015288:Neurokinin A