title: Synthesis and biological activity of FGLamide allatostatin analogs with Phe(3) residue modifications.
abstract: A FGLamide allatostatin neuropeptide mimic (H17) is a potential insect growth regulator which inhibits the production of juvenile hormone by the corpora allata. To find more evidence to reveal the structure-activity relationships of the Phe(3) residue in the C-terminal conserved pentapeptide and search for novel analogs with high activity, a series of Phe(3) residue-modified analogs were designed and synthesized using H17 as the lead compound. Bioassay using juvenile hormone (JH) production by corpora allata of the cockroach Diploptera punctata indicated that analogs 4, 11, and 13 showed strong ability to inhibit JH production in vitro, with IC50 of 38.5, 22.5, and 26 nM, respectively. As well, the activity of analog 2 (IC50 : 89.5 nM) proved roughly equivalent to that of H17. Based on the primary structure-activity relationships of Phe(3) residue, we suggest that for analogs containing six-membered aromatic rings, removing the methylene group of Phe(3) or an o-halogen or p-halogen-substituted benzene ring could increase the ability to inhibit biosynthesis of JH. This study will be useful for the design of new allatostatin analogs for insect management. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.
authors.affiliation: Department of Applied Chemistry, College of Science, China Agricultural University, Beijing, 100193, China.|Department of Cell and Systems Biology, University of Toronto, 25 Harbord St., Toronto, ON, M5S 3G5, Canada.|State Key Laboratory of the Discovery and Development of Novel Pesticide, Shenyang Sinochem Agrochemicals R&D Co. Ltd., Shenyang, 110021, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Xie
authors.affiliation: Department of Applied Chemistry, College of Science, China Agricultural University, Beijing, 100193, China.
authors.forename: Meizi
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Applied Chemistry, College of Science, China Agricultural University, Beijing, 100193, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Applied Chemistry, College of Science, China Agricultural University, Beijing, 100193, China.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Applied Chemistry, College of Science, China Agricultural University, Beijing, 100193, China.
authors.forename: Xinling
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Cell and Systems Biology, University of Toronto, 25 Harbord St., Toronto, ON, M5S 3G5, Canada.
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Tobe
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003058:Cockroaches / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D003335:Corpora Allata / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D005786:Gene Expression Regulation; D006727:Hormone Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D019476:Insect Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D007605:Juvenile Hormones / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D009479:Neuropeptides / Q000138:chemical synthesis* / Q000494:pharmacology; D057786:Peptidomimetics / Q000138:chemical synthesis* / Q000494:pharmacology; D010649:Phenylalanine / Q000737:chemistry / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D006727:Hormone Antagonists; D019476:Insect Proteins; D007605:Juvenile Hormones; D009479:Neuropeptides; D057786:Peptidomimetics; C076523:allatostatin; D010649:Phenylalanine
keywords: Phe3 residue modifications; allatostatins; biological activity; insect growth regulator; juvenile hormone