IMPROVED CYCLIC CRF ANTAGONISTS IMPROVED CYCLIC CRF ANTAGONISTS

摘要

Improved CRF antagonist peptides have the formula: (cyclo 30-33)DPheHisLeuLeuArgGluVal LeuGluNleAlaArgAlaGluGlnLeu IMAGE LeuNleGluIleIleNH2 wherein R30 is Cys or Glu; R33 is Cys, Lys or Orn; provided that when R30 is Cys, R33 is Cys and when R30 is Glu, R33 is Lys or Orn. The N-terminus may be extended by Asp-Leu-Thr. Lys may be substituted for Arg23 and its side chain connected by a lactam bridge to Glu20 to form a dicyclic peptide. Specific CRF antagonists disclosed include (cyclo 30-33) [D-Phe12, Nle21,38, Glu30, Lys33]rCRF(12-41); (cyclo 30-33) [D-Phe12, Nle21,38, Glu30, Orn33]rCRF(12-41), (cyclo 30-33) [D-Phe12, Nle21,38, Cys30,33]rCRF (12-41) and (bicyclo 20-23,30-33) [D-Phe12, Nle21,38, Lys23,33, Glu30]-rCRF(12-41).