Evaluation of Lactam-Bridged Neurotensin Analogues Adjusting ψ (Pro10) Close to the Experimentally Derived Bioactive Conformation of NT (8-13)

H Bittermann, J Einsiedel, H Hübner…

文献索引：Bittermann, Holger; Einsiedel, Juergen; Huebner, Harald; Gmeiner, Peter Journal of Medicinal Chemistry, 2004 , vol. 47, # 22 p. 5587 - 5590

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被引用次数: 34

摘要

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 (K i= ...