Synthesis, structure-activity relationship of nociceptin and its fragments

Nociceptin (NC) and its 4 fragments have been synthesized by solid phase peptide synthesis. Their hypertensive activity and mechanism, MVD assay and structure-activity relationship have been investigated. Results show that NC(1-13)NH2 is the smallest fragment that shares the same activity with NC. The truncation of C-terminal not only leads the decrease of receptor affinity but also the changes of receptor selectivity. The entire sequence may not be required for the full activity since NC(1-13)NH2 is as active as NC. Arg-Lys at the 12-13 position of C-terminal plays an important role in the activity of NC. The hypotensive activity of NC does not antagonize the hypertensive activity of renin-angiotensin system.