title: Structure-activity and conformational studies of a series of modified C-terminal hexapeptide neurotensin analogues.
abstract: Neurotensin (NT), is a linear tetradecapeptide (pGlu1-Leu2-Tyr3-Glu4-Asn5- Lys6-Pro7-Arg8-Arg9-Pro10-Tyr11-Ile12-Leu13) that has been found in the central nervous system and peripheral tissues and appears to have a variety of physiological properties. A C-terminal hexapeptide analogue [N alpha Me-Arg-Lys-Pro-Trp-Tle-Leu, (1) Tle = tert-leucine] has recently been reported to have high affinity for the NT receptor and appears to possess central activity after systemic administration. In an effort to probe the structure-activity and conformational properties of the dipeptide, Pro-Trp for binding and functional activity, these residues have been substituted with several natural and unnatural amino acids. Some of these analogues have binding affinities similar to compound 1, while in other cases, such as D-amino acid substitutions, the peptides had negligible binding affinity. In general, the Pro10 position seems more tolerant of substitution by amino acids that favor a reverse turn, rather than those that favor an extended conformation. The Trp11 position accepted extra steric bulk more readily than conformational constraints.
authors: Department of Chemistry, Warner-Lambert Co., Ann Arbor, Michigan.
authors: D L
authors: DL
authors: Heyl
authors: A M
authors: AM
authors: Sefler
authors: J X
authors: JX
authors: He
authors: T K
authors: TK
authors: Sawyer
authors: D J
authors: DJ
authors: Wustrow
authors: H C
authors: HC
authors: Akunne
authors: M D
authors: MD
authors: Davis
authors: T A
authors: TA
authors: Pugsley
authors: T G
authors: TG
authors: Heffner
authors: A E
authors: AE
authors: Corbin
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D007202:Indicators and Reagents; D051379:Mice; D009496:Neurotensin / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000378:metabolism; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry; D011487:Protein Conformation; D018028:Receptors, Neurotensin / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D007202:Indicators and Reagents; D009842:Oligopeptides; D018028:Receptors, Neurotensin; D009496:Neurotensin