Synthesis of constrained analogues of cholecystokinin/opioid chimeric peptides |
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Authors: | Ndungu John M Cain James P Davis Peg Ma Shou-W Vanderah Todd W Lai Josephine Porreca Frank Hruby Victor J |
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Affiliation: | a Department of Chemistry, University of Arizona, Tucson, AZ 85721, USA b Department of Pharmacology, University of Arizona, Tucson, AZ 85724, USA |
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Abstract: | In our ongoing research on the synthesis of constrained analogues of CCK/opioid chimeric peptides, a bicyclic dipeptide mimetic for Nle-Asp was designed and synthesized. Starting from β-allyl substituted aspartic acids, the terminal double bond was oxidized resulting in spontaneous cyclization to form racemic hemiaminals. Allylation of the hemiaminals afforded 5-allyl substituted proline analogues, which on oxidation, Horner-Emmons olefination, asymmetric hydrogenation, and bicyclization afforded bicyclic dipeptide mimetics for Nle-Asp. Constrained CCK/opioid peptide analogues containing bicyclic dipeptide mimetics for Nle-Gly, Nle-Asp, and homoPhe-Gly were then synthesized and analyzed at both the CCK and opioid receptors. |
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