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Peptide mimetics, alternatives strategies for pest control. - PS2122

Description
There is an ever-increasing pressure to reduce the impact of broad spectrum, neurotoxic pesticides (organophosphates, carbamates and synthetic pyrethroids) on human health and the environment and make their use more sustainable. To achieve this goal the levels of harmful active substances must be reduced by replacement with safer alternatives. Efforts have been made during the past 3 decades to develop insecticides with selective properties that act at specific targets in particular insect groups. This biorational approach has lead to the discovery of compounds that affect moulting and development in insects (eg juvenile hormone mimics, ecdysone agonists, chitin synthesis inhibitors) and compounds (nicotinoids) that act on the nervous system, but resistance is developing to some of these compounds. There is clearly a need for new biorational compounds with novel modes of action.

Aphids are some of the most economically important pests in the UK, causing direct damage to crops by feeding on young growing points of plants, but more importantly they have the ability to transmit numerous plant viruses that can result in serious reductions in crop yield. Two of the most damaging aphids in Britain are the pea aphid, Acyrthosiphon pisum, and the peach potato aphid Myzus persicae, which is considered the most important pest and virus vector aphid in the UK due to its wide host range and its proficiency in transmitting more than 120 plant viruses. Millions of pounds are spent each year on crop spraying and seeds treatments used to combat these pests, but problems are now being encountered due to the resistance aphids are developing to the pyrethroid pesticides used for their control.

Peptides from the insect endocrine system are the key regulators of virtually all physiological processes including feeding, growth, development, osmoregulation and reproduction, and are seen as an viable basis for the development of alternative strategies for biorational pest control. By applying peptides at inappropriate times it may be possible to disrupt the physiological processes they normally regulate, resulting in feeding suppression, retarded growth and development, and ultimately death. However, little progress in the utilisation of insect peptides has been made due to the problems associated with delivery and stability of these compounds. To exert their physiological effects peptides must be delivered to the insect blood to be transported to their target sites. However, unlike conventional insecticides that can be sprayed on a crop so that the chemical penetrates the insect cuticle or is consumed by the insects along with the plant material it eats, due to their chemical nature peptides cannot be applied by these methods. They are very susceptible to environmental conditions and do not readily penetrate the insect cuticle, and upon feeding would not only be rapidly degraded by the digestive enzymes in the gut, rendering them inactive, but would also have to pass through the gut wall to reach their sites of action. Modifications can be made to the structure of peptides to enhance their bioavailability. From previous work we have identified specific regions (amino acids) of selected feeding suppressive peptides that are susceptible to enzyme degradation and replaced these amino acids with mimics to increase their stability, and added molecules enhancing their uptake across the gut wall, whilst retaining their biological activity. Delivery of such peptide analogues to the insect blood via the gut or cuticle can be used to target the physiological processes the native peptide normally regulates (feeding) as an effective means of control. Much of this work was carrried out on Lepidoptera, from which hormonally active peptides could be readily identified.

This project aims to investigate the feeding of suppressive peptides of two pest aphid species, the peach potato aphid, M. persicae, and the pea aphid A. pisum. It will utilise available peptide analogues and design new analogues that will augment the effectiveness of these peptides. Using established aphid feeding assays, insecticidal peptides will be identified, and available peptide analogues tested for their feeding and developmental suppressive properties. The effects of gut enzymes on selected aphid peptides will be analysed to provide the necessary data for the design of new peptide analogues. The use of compounds such as absorbent enhancers will be utilised to increase the oral bioavailability of these peptide analogues. Effective peptide analogues will also be tested on other UK pest species (flies, beetles) to evaluate their wider application to reduce conventional, broad spectrum, neurotoxic pesticide use.
Objective
The primary aims of the proposed work are: (i) to take forward the major outputs from project PS2116 on the endocrine factors (neuropeptides) that regulate feeding, growth and development in insect pests and the key elements affecting their potential use in biorational pest control strategies. (ii) To utilise peptide mimetics to demonstrate that modified insect neuropeptide hormones provide new leads and offer viable alternatives to broad-spectrum neurotoxic pesticides. The specific objectives are:

1. To evaluate the best candidate lepidopteran peptides analogues (from project PS2116) for their insecticidal activity on aphids, using established feeding assays.

2. To identify additional insecticidal peptides from insect pest species by utilising available genomic databases and peptidomics.

3. Determine the major sites of proteolytic degradation in insecticidal neuropeptides (and analogues) to create new, more effective feeding suppressive peptide analogues. Assess the activity on pest aphid species, and investigate means to improve delivery and uptake.

4. To demonstrate the wider applicability of selected peptide analogues in other insect pest species such as dipterans and coleopterans and their potential to reduce broad-spectrum pesticide usage.

The project as outlined is based on a two-year work plan.

Project Documents
• Final Report : Peptide mimetics - alternative strategies for pest   (104k)
Time-Scale and Cost
From: 2008

To: 2010

Cost: £366,026
Contractor / Funded Organisations
Central Science Laboratory
Keywords
Biological Control              
Biological Effects              
Biopesticide              
Biotechnology              
Biotech-non GM              
Chemicals              
Crop Pests              
Genomics              
Minimisation              
Molecular Biology              
Natural              
Pest Control              
Pesticides              
Fields of Study
Pesticide Safety