Crf analogs

Details Crf analogs Crf analogs

C - Chemistry, Metallurgy

07

K

C07K 14/575 (2006.01) A61K 38/22 (2006.01) A61K 38/00 (2006.01)

Patent

CA 2086827

2086827 9221372 PCTABS00017 Analogs of CRF, which are based upon hCRF, oCRF and alpha-helical CRF, are disclosed that can be administered to achieve a substantial elevation of ACTH, .beta.-endorphin, .beta.-lipotropin, other products of the pro-opiomelanocortin gene and corticosterone levels. Analogs include those having the formula (see SEQ ID NO:9): Y-Ser-Xaa2-Glu-Pro-Pro-Ile-Ser-Leu-Asp-Leu-Thr-Phe-His-Leu-Leu-Arg-Glu-Val-Le_ u-Xaa20-Xaa21-Xaa22-Xaa23-Xaa24-Xaa25-Gl n-Leu-Ala-Gln-Gln-Ala-Xaa32-Ser-Asn-Arg-Lys-Leu-Xaa38-Xaa39-Ile-Xaa41-NH2, wherein Y is an acyl group having 7 or fewer carbon atoms or hydrogen; Xaa2 is Glu or Gln; Xaa20 is Ala or Glu; Xaa21 is Met or Nle; Xaa22 is Ala or Thr; Xaa23 is Arg or Lys; Xaa24 is D-Ala or Ala; Xaa25 is Glu or Asp; Xaa32 is D-His or His; Xaa38 is Met, Nle or Leu; Xaa39 is Ala, Glu or Asp; Xaa41 is Ile or Ala; provided however that at least one of Xaa20 and Xaa39 is Ala and that the N-terminus may be shortened by a sequence of up to about 5 residues. One example is [Ala20]-oCRF. These analogs or their pharmaceutically acceptable salts, dispersed in an acceptable liquid or solid carrier, can be administered to humans.

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