Cyclic analogs of insect oostatic peptides: Synthesis, biological activity, and NMR study

Cyclic peptides 2a-2c, derived from the sequence of the C-terminal shortene d analogs of the oostatic decapeptide H-Tyr-Asp-Pro-Ala-Pro-Pro-Pro-Pro-Pro -Pro-OH (1a), were synthesized and assayed on their effect in a reproductio n of the flesh fly Neobellieria bullata. The cyclization of the N-terminal linear tetra- and pentapeptides lb and le to the cyclotetra- and cyclopenta peptides 2b and 2c decreased the oostatic activity by one order of magnitud e. The cyclodecapeptide 2a, which emerged spontaneously during the pentapep tide cyclization, was quite inactive. Comparative H-1 and C-13 NMR study on a conformation of the cyclopeptides 2a-2c, and their linear precursors 1b and 1c revealed that a space structure of the cyclic analogues 2b and 2c is too restricted to adopt a biological conformation necessary for receptor b inding and therefore only minor oostatic activity is observed after their a pplication. The lack of the oostatic activity in the case of the more flexi ble dimeric analogue 2a is ascribed to the size of its molecule and its ove rall shape that is not compatible with a receptor binding. (C) 2001 Academi c Press.