Peptide Based Biopesticides

Het gebruik van insecticiden blijft zeer belangrijk omdat wereldwijd meer dan 75 miljard dollar verloren gaat door de vernietiging van oogsten door insecten Er zijn echter ernstige nadelen waaronder toenemende resistentie van insecten tegen insecticiden, ongewenste letaliteit van nuttige bestuivende insecten zoals bijen, en de aanwezigheid van insecticiden in het milieu (bodem en planten) als gevolg van slechte
(bio)afbraak. Het doel van dit voorstel was het ontwerpen en synthetiseren van biopesticiden op basis van peptiden. Dit moet leiden tot door de natuur geïnspireerde groene alternatieven voor insectenbestrijding.
"Peptiden" zijn de kleine equivalenten van "eiwitten" en biomoleculen, die aanwezig zijn in alle organismen. Ze worden op natuurlijke wijze biologisch, maar ook chemisch afgebroken in de bodem (water, warmte, UV, zuurstof, micro-organismen).
Er is een samenwerking tussen de HU en INNOVAPEPLINE opgezet. Innovapepline is een bedrijf dat zich richt op het ontwerp en de synthese van op peptiden gebaseerde biopesticiden en de toekomstige opschaling van hun synthese. De HU heeft gezorgd voor een praktische aanpak die inherent is aan de opleidingsdoelstellingen. De HU zorgt tevens voor inbreng van de noodzakelijke synthetische technologie, met inbegrip van apparatuur, menskracht en deskundigheid die vereist is voor het ontwerp en de synthese van op peptiden gebaseerde biopesticiden. Aldus werden nieuwe covalent reagerende, op peptide-gebaseerde, biopesticiden gesynthetiseerd, gebaseerd op recente belangrijke ontwikkelingen in covalente geneesmiddelen. Algemene methoden om de (bio)afbraaksnelheid te bepalen, werden ook ontwikkeld en zijn nu klaar voor gebruik. Recente evaluatie van deze verbindingen door SOLASTA BIO, een spin-out bedrijf van de Universiteit van Glasgow, heeft resultaten opgeleverd die bemoedigd zijn voor voortzetting van dit project. Daarom willen wij het ontwerp van onze verbindingen optimaliseren, gevolgd door biologische evaluatie en daaropvolgende chemische en biologische stabiliteitsstudies van veelbelovende kandidaten. Tevens willen we de opschalingsmogelijkheden verkennen. Onderzoek van deze aspecten is cruciaal voor de succesvolle ontwikkeling van biopesticiden op basis van peptiden.

Treatment of crops with insecticides remains essential because globally more than 75 billion dollars is lost through crop destruction by invasive insects. However, it is accompanied by severe disadvantages including increasing resistance of the target insects against insecticides, undesired lethality of beneficial pollinator insects like bees, and the presence of residual amount of insecticides in the environment (soil and plants), due to poor (bio)degradation. Therefore, the overall aim of this proposal was to design and synthesize peptide-based biopesticides. This should lead to Nature-inspired green alternatives for insect control. "Peptides" are the small equivalents of "proteins" and biomolecules, which are universally present in all organisms. They are naturally bio-degraded but also chemically degraded in the soil (water, heat, UV, oxygen, microorganisms).
A collaboration of the HU with INNOVAPEPLINE has been established. Innovapepline is a company that aims at the design and synthesis of peptide based biopesticides and future scaling-up of their synthesis. HU has provided a practical mind-set approach inherent to its education as well as the key synthetic technology including equipment, human power and expertise required for design and synthesis of peptide based biopesticides. Thus, new covalently interacting peptide-based biopesticides inspired by recent important developments of covalent drugs have been synthesized. General methods to monitor (bio)degradation rate have been also developed and are ready to use. Recent evaluation of these compounds at SOLASTA BIO spin-out company of the University of Glasgow) have shown promising results which are encouraging us to continue this project. Therefore, we wish to optimize the design of our compounds, followed by their biological evaluation and subsequent chemical and biological stability studies of promising candidates compounds, including investigation of scale up possibilities. These aspects are all crucial for successful development of peptide-based biopesticides.

Treatment of crops with insecticides remains essential because globally more than 75 billion dollars is lost through crop destruction by invasive insects. However it is accompanied by severe disadvantages including i. increasing resistance of the target insects against insecticides and ii. the undesired lethality of beneficial insects such as bees and other pollinator species. The significant reduction of insect species during the last years, at least partly caused by the presently available insecticides has also effects on insect-eating species. Last but not least the presence of residual amount of insecticides in the environment (soil and plants), because of poor (bio)degradation, is another distinct disadvantage. Therefore, the overall aim of this proposal is to design and synthesize peptide based biopesticides. This should lead to Nature inspired green alternatives for insect control because "Peptides" are the small equivalents of "proteins", that are biomolecules, which are universally present in all organisms and subject to their natural biodegradation mechanisms, as well as also chemically degraded in the soil (water, heat, UV, oxygen).
Design and synthesis of these environmentally benign compounds will eventually take place in a founded company called "INNOVAPEPLINE". Evaluation of candidate peptide based biopesticides can be carried out in collaboration with a recently founded company (spin-out of the University of Glasgow) called "SOLASTA BIO" (founders professors Shireen Davies, Julian Dow and Rob Liskamp) and/or with other (third) parties such as the University of Wageningen.
Upon recent identification of promising candidate compounds ("leads"), chemical optimization studies of leads will take place, followed by evaluation in field trials. In this proposal design, synthesis and chemical optimization of the biological activity of new peptides and development of methods to monitor their biodegradation rate will take place. Thereby expanding the repertoire of peptide based biopesticides. (292 words)