Insect neuropeptide antagonist. Part II. Synthesis and biological activityof backbone cyclic and precyclic PBAN antagonists

A new approach for the design and synthesis of pheromone biosynthesis activ ating neuropeptide (PBAN) agonists and antagonists using the backbone cycli zation and cycloscan concepts is described. Two backbone cyclic (BBC) libra ries were synthesized: library I (Ser library) was based on the active C-te rminal hexapeptide sequence Tyr-Phe-Ser-Pro-Arg-Leu-NH2 Of PBAN1-33NH(2); w hereas library II (D-Phe library) was based on the sequence of the PBAN lea d linear antagonist Arg-Tyr-Phe-D-PhePro-Arg-Leu-NH2. In both libraries the Pro residue was replaced by the BBC building unit N-alpha-(omega -aminoalk yl) Gly having various lengths of alkyl chain. The peptides of the two libr aries were tested for agonistic and antagonistic activity. Four precyclic p eptides based on two of the BBC antagonists were also synthesized; their ac tivity revealed that a negative charge at the N-terminus of the peptide abo lished antagonistic activity. We also describe the use of the reagent SiCl( 3)l for selective deprotection of the Boc group from the building unit prio r to on-resin amino-end to backbone-nitrogen (AE-BN) cyclization, during so lid-phase synthesis with Fmoc chemistry.