Peptidomimetics in the Discovery of New Insect Growth Regulators: Studies on the Structure−Activity Relationships of the Core Pentapeptide Region of Allatostatins

• Published in: Journal of agricultural and food chemistry Vol. 59; no. 6; pp. 2478 - 2485
• Main Authors: Kai, Zhen-peng, Xie, Yong, Huang, Juan, Tobe, Stephen S, Zhang, Jin-rui, Ling, Yun, Zhang, Li, Zhao, Yi-chen, Yang, Xin-ling
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 23.03.2011; Amer Chemical Soc
• Subjects: Agriculture; Agriculture, Multidisciplinary; Amino Acid Sequence; Animals; Biological and medical sciences; Chemistry; Chemistry, Applied; Cockroaches - drug effects; Cockroaches - physiology; Crop and Animal Protection Chemistry; Female; Food industries; Food Science & Technology; Fundamental and applied biological sciences. Psychology; Juvenile Hormones - chemical synthesis; Juvenile Hormones - chemistry; Juvenile Hormones - pharmacology; Life Sciences & Biomedicine; Male; Molecular Sequence Data; Molecular Structure; Neuropeptides - chemical synthesis; Neuropeptides - chemistry; Neuropeptides - pharmacology; Oligopeptides - chemistry; Oligopeptides - pharmacology; Peptidomimetics - chemistry; Physical Sciences; Science & Technology; Structure-Activity Relationship; analogues; pentapeptide; allatostatins; structure−activity relationships; peptidomimetics; juvenile hormone; Insect growth regulators; DESIGN; ANALOGS; JUVENILE-HORMONE BIOSYNTHESIS; HEMOLYMPH; INHIBITION; structure-activity relationships; CORPORA-ALLATA; COCKROACH DIPLOPTERA-PUNCTATA; Growth; Insecta; Discoveries; Regulator; Structure activity relation; Arthropoda; Analog; Invertebrata; Pentapeptide; Juvenile hormone
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/jf200085d

Cockroach-type allatostatins (ASTs) were discovered in cockroaches through their capacity to inhibit the production of juvenile hormone by the corpora allata (CA). ASTs were considered as potential insect growth regulator (IGR) candidates, but several disadvantages, including the absence of the effect in vivo and rapid degradation in vivo, precluded their application in pest management. The CA were selected as the target, and the core pentapeptide region (YDFGL) was chosen as the lead sequence in the search for new IGRs based on the allatostatins. We designed and synthesized 24 analogues, which mimicked each amino acid of the core region, to determine structure−activity relationships and the possibility of shortening the ASTs in the core region while retaining activity. The results suggest that the sequence FGLa is more important than Y/FX because Y/FX mimics show strong effects in vitro and in vivo. In particular, compound I3 was synthesized by substitution of Y/FX with 6-phenylhexnoic acid and exhibits higher activity in vitro than the complete core region. Furthermore, compound I3 has a clear effect in vivo on juvenile hormone (JH) biosynthesis of Diploptera punctata females, providing a possible application for cockroach management. On the basis of the structure−activity relationship of pentapeptide analogues, a general structure of potential potent AST analogues is proposed here. A new approach using peptidomimetics in the discovery of IGRs is demonstrated in our study.