1. Competitive antagonists of the corticotropin releasing factor (CRF) scanned with a i-(i+3) Glu Lys Bridge
- Author
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Jean Rivier, Anne Z. Corrigan, Antonio Miranda, Charleen Miller, A. G. Craig, Steven C. Koerber, S L Lahrichi, Catherine Rivier, J. Gulyas, Wylie Vale, and Steve Sutton
- Subjects
chemistry.chemical_classification ,medicine.medical_specialty ,Chemistry ,Sauvagine ,Central nervous system ,Peptide ,Human sequence ,Endocrinology ,Bridge (graph theory) ,medicine.anatomical_structure ,Internal medicine ,medicine ,Urotensins ,Receptor ,Predictive methods - Abstract
CRF [1] is involved in a wide spectrum of central nervous system (CNS)-mediated effects, suggesting that this peptide plays an important role within the brain, especially in response to stressful stimuli [2]. Systematic SAR investigations have resulted in the development of CRF antagonists such as [3], members of the (standard) family [4] and conformationally restricted analogs [5] that are effective in the CNS. Those results, predictive methods and physicochemical measurements have suggested that CRF and its family members (urotensins and sauvagine) assume an conformation when interacting with the CRF receptors. To further test this hypothesis, we have scanned the whole rat/human sequence with an i-(i + 3) bridge consisting of the Glu-Xaa-Xbb-Lys scaffold which we and others had shown to be compatible with maintenance or enhancement of structure in at least some unpredictable cases.
- Published
- 2005
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