ABSTRACT
Insect kinin neuropeptides are pleiotropic peptides that are involved in the regulation of hindgut contraction, diuresis, and digestive enzyme release. They share a common C-terminal pentapeptide sequence of Phe(1)-Xaa(2)-Yaa(3)-Trp(4)-Gly(5)-NH2 (where Xaa(2) = His, Asn, Phe, Ser, or Tyr; Yaa(3) = Pro, Ser, or Ala). Recently, the aphicidal activity of insect kinin analogues has attracted the attention of researchers. Our previous work demonstrated that the sequence-simplified insect kinin pentapeptide analogue Phe-Phe-[Aib]-Trp-Gly-NH2 could retain good aphicidal activity and be the lead compound for the further discovery of eco-friendly insecticides which encompassed a broad array of biochemicals derived from micro-organisms and other natural sources. Using the peptidomimetics strategy, we chose Phe-Phe-[Aib]-Trp-Gly-NH2 as the lead compound, and we designed and synthesized three series, including 31 novel insect kinin analogues. The aphicidal activity of the new analogues against soybean aphid was determined. The results showed that all of the analogues exhibited aphicidal activity. Of particular interest was the analogue II-1, which exhibited improved aphicidal activity with an LC50 of 0.019 mmol/L compared with the lead compound (LC50 = 0.045 mmol/L) or the commercial insecticide pymetrozine (LC50 = 0.034 mmol/L). This suggests that the analogue II-1 could be used as a new lead for the discovery of potential eco-friendly insecticides.
Subject(s)
Insecticides/chemistry , Insecticides/toxicity , Kinins/chemistry , Kinins/toxicity , Amino Acid Sequence , Animals , Aphids/drug effects , Drug Design , Insecticides/chemical synthesis , Kinins/chemical synthesis , Molecular Sequence Data , Structure-Activity RelationshipABSTRACT
Kinins are polypeptides of 9-18 amino-acid residues containing a bradykinin-like sequence, in some cases as part of a molecule. The bradykinin-like sequence is either bradykinin, Hyp3-bradykinin or Thr6-bradykinin. Kinins are neurotoxic components of wasp and ant venoms, causing in the insect CNS a presynaptic block of the cholinergic transmission by means of an irreversible depletion, probably caused by a non-competitive inhibition of choline uptake.
Subject(s)
Ant Venoms/chemistry , Kinins/toxicity , Nervous System/drug effects , Neurotoxins/chemistry , Wasp Venoms/chemistry , Amino Acid Sequence , Animals , Bradykinin/chemistry , Kinins/chemistry , Molecular Conformation , Molecular Sequence Data , Muscle, Smooth/drug effects , Synapses/drug effectsABSTRACT
1. In co-operation with colleagues in Europe, Japan and the U.S.A., 25 years of research in Amsterdam have provided new views on the way some hymenopteran insects incapacitate their prey by a diversity of neurotoxins, resulting in block of synaptic transmission in CNS or neuromuscular junctions, or affecting voltage dependent phenomena in nerve and muscle fibers. 2. Nicotinic synaptic transmission in the insect CNS is irreversibly blocked at the presynaptic side by kinins, or reversibly and postsynaptically blocked by philanthotoxins. 3. Glutamatergic neuromuscular transmission is reversibly blocked by philanthotoxins at the pre- and/or postsynaptic side. 4. A presynaptic block of neuromuscular transmission was found with the Microbracon toxins. 5. An irreversible deactivation, without paralysis, of cockroaches is caused by a sting of Ampulex compressa into the suboesophageal ganglion. 6. Poneratoxin, a 25 amino acid residue polypeptide, isolated from an ant venom, is the first described hymenopteran neurotoxin affecting excitability of nerve and muscle fibres by changing the kinetics of the voltage-dependent sodium channel.
