CONFORMATIONALLY CONSTRAINED BACKBONE-CYCLIZED PEPTIDE ANALOG

摘要

PROBLEM TO BE SOLVED: To provide a novel backbone-cyclized analog comprising a peptide sequence containing at least two building units.

SOLUTION: The backbone-cyclized peptide analog is formed by means of bridging groups bonded via the alpha nitrogen atoms of an amino acid derivative to provide novel nonpeptidic linkages. The novel building units are Nα/(ω-functionalized) amino acids constructed to include a spacer and a terminal functional group. One or more of these Nα/(ω-functionalized) amino acids are incorporated into a peptide sequence, preferably during solid phase peptide synthesis. The reactive terminal functional groups are protected by specific protecting groups that can be selectively removed to effect either backbone-to-backbone or backbone-to-side chain cyclizations. The peptide analog is exemplified by a backbone-cyclized bradykinin antagonist having biological activity. A further embodiment is somatostatin analog having one or two ring structures involving main chain cyclization.

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