Insertion of 2-carboxysuccinate and tricarballylic acid fragments into cyclic-pseudopeptides: new antagonists for the human tachykinin NK-2 receptor.
A series of cyclic pseudopeptides were synthesized containing the sequence -Trp-Phe-(D)-PhePsiCH2NH-, the terminal ends of which were bound to 2-carboxy succinate or enantiomerically enriched tricarballylic acid to give the final cyclic structures. These two molecules and their subsequent derivatives were screened for h-NK2 receptor binding and functional antagonist activity on the rabbit urinary bladder.
Harmat
Nicholas J S
NJ
Menarini Ricerche S.p.A. Laboratori di Firenze, Via Rismondo 12/A, 50131 Firenze, Italy. chimfarm@menarini.ricerche.it
Giannotti
Danilo
D
Nannicini
Rossano
R
Perrotta
Enzo
E
Criscuoli
Marco
M
Patacchini
Riccardo
R
Renzetti
Anna-Rita
AR
Giuliani
Sandro
S
Altamura
Maria
M
Maggi
Carlo A
CA
D000818:Animals; D003500:Cyclization; D018716:Molecular Mimicry; D009842:Oligopeptides / Q000138:chemical synthesis / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000494:pharmacology; D011817:Rabbits; D011869:Radioligand Assay; D018041:Receptors, Neurokinin-2 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D019802:Succinic Acid / Q000737:chemistry; D014233:Tricarboxylic Acids / Q000737:chemistry; D001743:Urinary Bladder / Q000187:drug effects
D009842:Oligopeptides; D010456:Peptides, Cyclic; D018041:Receptors, Neurokinin-2; D014233:Tricarboxylic Acids; D019802:Succinic Acid; C028021:tricarballylic acid