title: Rational design of novel neurotensin mimetics: discovery of a pharmacologically unprecedented agent exhibiting concentration-dependent dual effects as antagonist and full agonist.
abstract: We report the rational design of novel neurotensin mimetics through use of the Multiple Template Approach. This approach is based on our notion that a flexible peptide can be replaced by a partially flexible molecule, identified through testing a comparatively small number of molecules possessing a different intrinsic availability of conformations of the native peptide. The Multiple Template Approach has culminated in the discovery of a pharmacologically unprecedented agent, which behaves as a neurotensin antagonist at low concentration and as a full neurotensin agonist at high concentration.
authors: Mayo Foundation for Medical Education and Research, Jacksonville, FL 32224.
authors: Y P
authors: YP
authors: Pang
authors: J
authors: J
authors: Zaidi
authors: A P
authors: AP
authors: Kozikowski
authors: B
authors: B
authors: Cusack
authors: E
authors: E
authors: Richelson
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D015195:Drug Design; D066298:In Vitro Techniques; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009496:Neurotensin / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000737:chemistry; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D018028:Receptors, Neurotensin / Q000187:drug effects / Q000378:metabolism
chemical_list: D010455:Peptides; D018028:Receptors, Neurotensin; D009496:Neurotensin