Evaluation of Lactam-Bridged Neurotensin Analogues Adjusting ψ(Pro10) Close to the Experimentally Derived Bioactive Conformation of NT(8−13)
- 29 September 2004
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Medicinal Chemistry
- Vol. 47 (22) , 5587-5590
- https://doi.org/10.1021/jm049644y
Abstract
The neurotensin C-terminal hexapeptide, NT(8−13), which has been found to adopt a β-strand-like conformation while bound to the NT1 receptor, was modified by the introduction of conformational constraints. Synthesis of the four stereoisomeric 4.4-spirolactams 1 − 4 and subsequent NT1 receptor binding studies showed that the restriction of ψ(Pro10) to approximately 130° leads to a more than 1000-fold increase of binding affinity for 1 (Ki = 12 nM) when compared to the more flexible analogue [NMeTyr11]NT(8−13).Keywords
This publication has 17 references indexed in Scilit:
- The conformation of neurotensin bound to its G protein-coupled receptorProceedings of the National Academy of Sciences, 2003
- Novel Bioactive and Stable Neurotensin Peptide Analogues Capable of Delivering Radiopharmaceuticals and Molecular Beacons to TumorsJournal of Medicinal Chemistry, 2003
- The effects of systemic NT69L, a neurotensin agonist, on baseline and drug-disrupted prepulse inhibitionBehavioural Brain Research, 2003
- Neurotensin: peptide for the next millenniumRegulatory Peptides, 2000
- Identification of Residues Involved in Neurotensin Binding and Modeling of the Agonist Binding Site in Neurotensin Receptor 1Published by Elsevier ,2000
- Synthesis and Human Neurotensin Receptor Binding Activities of Neurotensin(8−13) Analogues Containing Position 8 α-Azido-N-alkylated Derivatives of Ornithine, Lysine, and HomolysineJournal of Medicinal Chemistry, 1999
- Preparation and receptor binding affinities of cyclic C-terminal neurotensin (8–13) and (9–13) analoguesBioorganic & Medicinal Chemistry Letters, 1999
- Design and Structure-Activity Relationships of C-Terminal Cyclic Neurotensin Fragment AnalogsJournal of Medicinal Chemistry, 1995
- Synthesis, conformational properties, and antibody recognition of peptides containing .beta.-turn mimetics based on .alpha.-alkylproline derivativesJournal of Medicinal Chemistry, 1991
- Potent and highly selective neurokinin antagonistsJournal of Medicinal Chemistry, 1990