Int.J.Curr.Microbiol.App.Sci (2019) 8(2): 869-878 International Journal of Current Microbiology and Applied Sciences ISSN: 2319-7706 Volume 8 Number 02 (2019) Journal homepage: http://www.ijcmas.com Review Article https://doi.org/10.20546/ijcmas.2019.802.098 Neuropeptides as Novel Insecticidal Agents K. Elakkiya, P. Yasodha*, C. Gailce Leo Justin and Vijay Akshay Kumar Anbil Dharmalingam Agricultural College & Research Institute, Navalur Kuttapattu, Trichy–620027 Tamil Nadu, India *Corresponding author ABSTRACT Neuropeptides (protein molecules) are synthesised in the neurons, helps to communicate the impulse from the stimulant to the receptor. Neuropeptides are responsible for regulating a various physiological functions including development, metabolism, water and ion homeostasis, and as neuromodulators in circuits of the central nervous system. Neuropeptides are different from neurotransmitters because, former releases in the haemolymph and the later releases in the neuro-neuro junction or in the neuro-muscular K e yw or ds junction. The first neuropeptide isolated from Periplanata Americana was protocolin in the year 1975 which helps in muscle contractions in hindgut, reproductive, skeletal and Insect neuropeptide, heart muscle. At present a total of 4782 insect neuropeptide records were obtained which PBAN, backbone cyclic perform various related physiological functions. Thus it paves the way for the generation of novel type of putative insect control agents based on backbone cyclic (BBC) peptidomimetic antagonists peptidomimetic antagonists of insect-neuropeptides. At present four different neuropeptides such as proctolin, kinin, pheromone biosynthesis activating neuropeptide Article Info (PBAN) and allatostatin were studied thoroughly and their biologically active sequence Accepted: were identified. Using this sequence peptidomimetic analogues (either as agonists or 07 January 2019 antagonists) were synthesized in automated peptide synthesizer and tested for their Available Online: efficacy as insecticide. Among those four PBAN showed good result as insecticide by 10 February 2019 reducing pheromone production up to 73% in Helicoverpa peltigera. Based on this many neuropeptides were under in vitro test for their antagonist activity. In 2016, a synthetic antagonistic neuropeptide based on pheromone biosynthesis activating neuropeptide was registered for patent by Altstein. This neuropeptide based insecticide is highly insect specific and can be incorporated as apart in integrated pest management though the production of synthetic peptide is critical. Introduction To overcome those difficulties, strategies were approached based on integrated pest To meet the requirements of population green management which includes the revolution has started which results in the use characteristics of insect specific, non toxic, of toxic chemicals and insects too gained compatible with other insect control agents, resistance to overcome these toxic substances. etc. Initially to meet these requirements Continuous use of those toxic substances in various compounds such as bio control turn results in the degradation of environment. agents, newer insecticides, transgenic plants 869 Int.J.Curr.Microbiol.App.Sci (2019) 8(2): 869-878 were introduced. Now a days insects are by Coast and Schooley (2011). gaining resistance to those compounds and so an innovative approach for pest management Families of neuropeptide such as neuropeptide based pest control were established. Neuropeptides are the At present, roughly 54 insect neuropeptide neurohormones which are synthesised in the families were classified which covers 23 neurons or neuro endocrine cells and are insect orders. Among those 54 neuropeptide released in the haemolymph. Neuropeptides families only four neuropeptides (Proctolin, coordinates complex of physiological kinin, pheromone biosynthesis activating functions like mating, oviposition, moulting, neuropeptide and allatostatin) were studied water balance, fat mobilization, etc. (Yeoh et thoroughly and tested for their bioassay al., 2017). Neuropeptides are produced from activity against various insects (Table 1). larger precursor proteins which are known as prepropeptides. Prepropeptide comprise of a Steps involved in isolation of signal peptide (which directs the protein to the neuropeptide:n secretary pathway), progenitors of mature peptides (the biologically active peptides), Sequencing of protein is done by isolating the spacer peptides (peptide fragments with no specific gene of interest using AQUA and known biological function and non conserved PROCHECK-NMR (Laskowski et al., 1996). sequences) and cleavage sites (monobasic and Then artificial synthesis of peptide is done by dibasic) (Yeoh et al., 2017). The first the condensation reaction of the carboxyl neuropeptide isolated was proctolin from group of one amino acid to the amino cockroach which was found to have group of another using Fmoc myostimulatory activity (Starratt and Brown, (fluorenylmethoxycarbonyl) resin (Shin et al., 1975). One year later AKH, the adipokinetic 1999). After isolation, in vitro and in vivo hormone of Locusta migratoria was found. protein docking is done using various AKH-related peptides have now been softwares such as ADAM, AutoDock, identified in numerous insects, and several DARWIN, DIVALI, DOCK, DockVision, other protostomes including arthropods, EUDOC, FlexX, FLOG, FTDOCK, GOLD, nematodes, annelids and mollusks (Gade, Hammerhead, ICM, LIGIN, LUDI, 1997). MCDOCK, Prodock, Proleads, QXP, SANDOCK, etc. (Sousa et al., 2006). Only with the advent of genomics, protein Structural modification of synthesised protein mass spectrometry and high-field NMR is done to obtain the antagonist activity either spectroscopy in the late 1980s and 1990s by Linear replacement /side chain knowledge on insect neuropeptides was modification (Fig. 1) or by backbone increased. Later in the year 1989 PBAN was cyclization (Fig. 2) (Gilon et al., 1997).The found to regulate sex pheromone synthesis in final product is produced in the form of dry female moths (Raina et al., 1989) with this powder (Alstein, 2003). the knowledge on insect neuropeptide has been increased. Neuropeptides were classified Proctolin into different families based on the homology of amino acid sequence. In order to Proctolin is produced by motor neurons in standardize classification of neuropeptides, locusts and found to regulate corpora cardiac DINeR (Database for Insect Neuropeptide crawling behaviour in Drosophila (Clark et Research) adopts the nomenclature for al., 2006). The biologically active sequence of naming insect neuropeptide families proposed proctolin contains arginin, tyrosine, leucine, 870 Int.J.Curr.Microbiol.App.Sci (2019) 8(2): 869-878 threonine (Fig. 3). Replacing an amino group to Bombyx mori as diapause hormone. C- with O2 between Tyr2 and Leu3 was almost terminal hexapeptide, H-Tyr-Phe-Ser-Pro- found to inactivate the muscle contraction in Arg-Leu-NH2, the active sequence of PBAN Locusta migratoria at a concentration of 1 was found to dissolve in the solvent and mmol/L. Replacing an amino group with O2 hence choosed for insecticidal activity. The between Arg1 and Tyr2 was found to retained peptide H-Arg-Tyr-Phe-D-Phe-Pro-Arg-Leu- the activity of muscle O2 significantly. NH 2 exhibited the highest antagonistic Cyclization of proctolin (Cycloproctolin) was activity is because when using dextro (d) phe. found to be a potent antagonist of proctolin- It caused jitters action in insect. Injection of induced production of the second messengers 100 pmol of this peptide, inhibited sex InsP3 (insulin P3) and InsP4 (insulin P4) pheromone biosynthesis by 63% after 2 h (Scherkenbeck, 2009). (Gilon et al., 1997). Based on substitution of l-amino acids with d-Phe followed by Kinins backbone cyclization (Fig. 4), has led to the discovery of several highly potent linear and The first members of the kinin family was conformationally constrained, selective, isolated from Leucophaea maderae also metabolically stable backbone cyclic (BBC) found to be present in nematodes, annelids pure antagonists for PBAN (Harinton, 2010). and molluscs (Radford et al., 2002) triggers ecdysis behaviour. Kinin shares a common C- Allatostatin –A, B, C terminal pentapetide sequence of Phe-Phe- Aib- Trp- Gly-NH2. When Gly is replaced The first member of the insect AST family using any of the following substitute and its was isolated in the year 1989 from brain aphicidal activity was tested (Zang, 2015). extracts of the cockroach Diploptera punctata (Woodhead et al., 1989). AST is Pyrokinins /pheromone biosynthesis found to be three types. AST-A as cockroach activating neuropeptides (PBANs) type, AST- B as cricket type and AST C as moth type. These peptides were called Pheromone Biosynthesis Activating allatostatins due to their ability to inhibit Neuropeptide (PBAN) regulates pheromone juvenile hormone (JH) biosynthesis by the biosynthesis and is a peptide of pyrokinin corpora allata. AST also regulates various type. Since no PK precursor gene was yet aspects of feeding and metabolism in several known these peptides were named after their species (Yeoh et al., 2017). Allatostatins functions: Pheromone Biosynthesis contains 8-13 amino acids and are amidated. Activating Neuropeptides (PBAN), Diapause The biologically active peptide sequences of Hormone (DH), Melanization and Reddish allatostatin are Ala-Pro-Ser-Gly-Ala-Gln- Coloration Hormone (MRCH) and so on. Arg-Leu-Tyr-Gly-Phe Gly-Leu- NH2. An in PBAN and DH were