Your browser doesn't support javascript.
loading
Phyto-inspired cyclic peptides derived from plant Pin-II type protease inhibitor reactive center loops for crop protection from insect pests.
Saikhedkar, Nidhi S; Joshi, Rakesh S; Yadav, Amit K; Seal, Shubhendu; Fernandes, Moneesha; Giri, Ashok P.
Afiliación
  • Saikhedkar NS; Biochemical Sciences Division, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune 411008, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.
  • Joshi RS; Institute of Bioinformatics and Biotechnology, Savitribai Phule Pune University, Pune 411007, India.
  • Yadav AK; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India; Organic Chemistry Division, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune 411008, India.
  • Seal S; John F. Welch Technology Centre, GE Healthcare, Bangalore 560066, India.
  • Fernandes M; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India; Organic Chemistry Division, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune 411008, India.
  • Giri AP; Biochemical Sciences Division, CSIR-National Chemical Laboratory, Dr. Homi Bhabha Road, Pune 411008, India; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India. Electronic address: ap.giri@ncl.res.in.
Biochim Biophys Acta Gen Subj ; 1863(8): 1254-1262, 2019 08.
Article en En | MEDLINE | ID: mdl-31077794
BACKGROUND: Natural defence of plants against insect pests involves protease inhibitors (PIs) that interfere with insect digestive proteases. Pin-II type plant PIs are wound inducible upon insect damage and possess multiple inhibitory repeat domains that can inhibit trypsin and chymotrypsin-like proteases in the insect midgut. Yet, their agricultural ex-vivo application is limited due to large molecular size and environmental instability, which could be overcome by small peptides. METHODS: Bicyclic peptides were designed by grafting Pin-II PIs derived reactive center loop (RCL) on synthetic tris(bromomethyl)benzene scaffold. In vitro binding with trypsin-like proteases was evaluated by biochemical and biophysical assays, followed by molecular dynamics simulations. In vivo effects on two major lepidopteran insect pests, Helicoverpa armigera and Spodoptera litura were studied upon feeding with peptide treated leaves. Affinity based pull down assays were used to identify target proteins in insect gut. RESULTS: Bicyclic RCLs showed ten-fold enhanced protease inhibition compared to their linear counterparts. They exhibited feeding deterrence and growth reduction of lepidopteran insects. Bicyclic peptides predominantly interact with midgut serine proteases. Possible binding modes involve simultaneous interaction with the active site and specificity-determining residues of insect gut trypsin. CONCLUSION: Bicyclic peptides are potent inhibitors of serine proteases in the insect midgut. They cause feeding aversion and larval growth retardation. Bi-domain cyclic peptides interact with two sites on trypsin, leading to enhanced efficacy over linear RCL peptides. GENERAL SIGNIFICANCE: Bicyclic peptides mimic natural PIs by inhibiting insect proteases leading to growth reduction, thus, could be used as pest control molecules in agriculture.
Asunto(s)
Palabras clave

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Péptidos Cíclicos / Proteínas de Plantas / Inhibidores de Proteasas / Productos Agrícolas / Lepidópteros Límite: Animals Idioma: En Revista: Biochim Biophys Acta Gen Subj Año: 2019 Tipo del documento: Article País de afiliación: India Pais de publicación: Países Bajos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Péptidos Cíclicos / Proteínas de Plantas / Inhibidores de Proteasas / Productos Agrícolas / Lepidópteros Límite: Animals Idioma: En Revista: Biochim Biophys Acta Gen Subj Año: 2019 Tipo del documento: Article País de afiliación: India Pais de publicación: Países Bajos