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J Med Chem. 2004 Jun 17;47(13):3450-4.

Determinants of corticotropin releasing factor. Receptor selectivity of corticotropin releasing factor related peptides.

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Health Care Research Center, Procter & Gamble Pharmaceuticals, 8700 Mason-Montgomery Road, Mason, Ohio 45040, USA.

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  • J Med Chem. 2005 Nov 17;48(23):7502. Tcheiner, Michelle [corrected to Tscheiner, Michelle].


The corticotropin-releasing factor (CRF) peptide family is an important target in pharmaceutical research. The CRF system consists of two receptors, corticotropin releasing factor receptor 1 (CRF1R) and corticotropin releasing factor receptor 2 (CRF2R), a nonreceptor binding protein, and the peptide agonists of these receptors. The recent discovery of the CRF2R selective peptide agonists, UCN2, UCN3 and URP, prompted investigations into the structural source of CRF1R versus CRF2R selectivity of CRF peptide family members. Data from chimeric peptides demonstrated that amino acids in the N-terminus and C-terminus of CRF, UCN1, UCN2 and Sauvagine peptide families influence CRFR selectivity. Analysis of specific amino acid residues in the N-terminus and C-terminus demonstrated that the presence of a proline at position 11 and alanine at positions 35 and 39 (hCRF numbering) decreases CRF1R activity and increases CRF2R selectivity in CRF, UCN1 and sauvagine peptides. The availability of a large group of selective and nonselective CRF receptor peptide agonists will facilitate the development of CRF receptor selective drugs.

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