STRUCTURE-ACTIVITY STUDIES OF ALLATOSTATIN-4 ON THE INHIBITION OF JUVENILE-HORMONE BIOSYNTHESIS BY CORPORA-ALLATA - THE IMPORTANCE OF INDIVIDUAL SIDE-CHAINS AND STEREOCHEMISTRY

The production of juvenile hormone III (JH III) by the corpora allata of the cockroach Diploptera punctata is regulated in part by peptides originating from the brain. One group of these peptides, termed allato statins, reversibly inhibits the biosynthesis of JH in vitro. Allatost atin 4 (AST4: Asp-Arg-Leu-Tyr-Ser-Phe-Gly-Leu-amide) is the smallest m ember of the AST family yet defined and was used as the benchmark pept ide for these initial structure-activity studies. Two initial analog s eries of AST4 were examined for the ability of each analog to inhibit JH biosynthesis by corpora allata in vitro. Each analog series consist ed of analogs that contained a single amino acid change from the nativ e AST4 sequence. The first series contained Ala replacement analogs an d the second contained analogs with D-amino acid replacements. The fir st analog series used Ala replacements to help indicate which amino ac id side chains were most important for inhibition of JH biosynthesis. The most important side chain appeared to be Leu(8) followed by Phe(6) and Tyr(4). Additionally, the D-amino acid series suggested that a se condary structural element(s) at the C-terminus of AST4 could be impor tant to the biological activity.