| 摘要 |
Novel cyclic CRF antagonist peptides are created by shortening the N-terminus of a CRF family peptide by 8-11 residues and adding an acyl group. CML is preferably present in what would be the 27-position of the native CRF sequence, and D-Tyr may be incorporated at the N-terminus to facilitate labelling. The cyclizing bond is preferably created between the side chains of the residues in positions 30 and 33; but it may alternatively be created between the residues in either of positions 28 and 29 with those in positions 31 and 32 or with those in positions 32 and 33, respectively. The side chain of Lys in position 33 is preferably linked to the side chain of Glu in position 30 by a lactam bridge to form the cyclic peptide. Disclosed CRF antagonists include: (cyclo 30-33) [Ac-Asp9, D-Phe12, Nle21,38, CML27,40, Glu30, Lys33]r/hCRF(9-41), (cyclo 30-33) [Ac-Asp9, D-Phe12, Nle21,38, CML27,37, Glu30, Lys33]r/hCRF(9-41), (cyclo 30-33) [Ac-Asp9, D-Phe12, CML14,27, Nle21,38, Glu30, Lys33]r/hCRF(9-41), (cyclo 30-33) [Ac-Asp9, D-Phe12, Nle21,38, CML27, Glu30, Lys33]r/hCRF(9-41), (cyclo 30-33) [Ac-Asp9, D-Phe12, CML18,27, Nle21,38, Glu30, D-His32, Lys33]r/hCRF(9-41) and (cyclo 30-33) [Ac-Asp9, D-Phe12, CML18,27, Nle21,38, Glu30, Lys33]r/hCRF(9-41).
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