A C-terminal aldehyde insect kinin analog enhances inhibition of weight gain and induces significant mortality in Helicoverpa zea larvae

Nachman, Ronald J.; Coast, Geoffrey M.; Douat, Céline; Fehrentz, Jean Alaín; Kaczmarek, Krzysztof; Zabrocki, Janusz; Pryor, Nan W.; Martinez, Jean

doi:10.1016/j.peptides.2003.06.008

Cited by 34 publications

(24 citation statements)

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“…One biostable kinin peptidomimetic containing aminoisobutyric acid, 1728, has potency similar to or higher than the aedeskinins on recombinant receptors (12). Such biostable kinin analogs have potential in the control of insect pests because they reduce feeding in lepidopteran larvae (10,13) and increase aphid mortality (14,15).…”

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confidence: 99%

Leucokinin mimetic elicits aversive behavior in mosquito Aedes aegypti (L.) and inhibits the sugar taste neuron

Kwon

Agha

Smith

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Insect kinins (leucokinins) are multifunctional peptides acting as neurohormones and neurotransmitters. In females of the mosquito vector Aedes aegypti (L.), aedeskinins are known to stimulate fluid secretion from the renal organs (Malpighian tubules) and hindgut contractions by activating a G protein-coupled kinin receptor designated "Aedae-KR." We used protease-resistant kinin analogs 1728, 1729, and 1460 to evaluate their effects on sucrose perception and feeding behavior. In no-choice feeding bioassays (capillary feeder and plate assays), the analog 1728, which contains α-amino isobutyric acid, inhibited females from feeding on sucrose. It further induced quick fly-away or walk-away behavior following contact with the tarsi and the mouthparts. Electrophysiological recordings from single long labellar sensilla of the proboscis demonstrated that mixing the analog 1728 at 1 mM with sucrose almost completely inhibited the detection of sucrose. Aedae-KR was immunolocalized in contact chemosensory neurons in prothoracic tarsi and in sensory neurons and accessory cells of long labellar sensilla in the distal labellum. Silencing Aedae-KR by RNAi significantly reduced gene expression and eliminated the feeding-aversion behavior resulting from contact with the analog 1728, thus directly implicating the Aedae-KR in the aversion response. To our knowledge, this is the first report that kinin analogs modulate sucrose perception in any insect. The aversion to feeding elicited by analog 1728 suggests that synthetic molecules targeting the mosquito Aedae-KR in the labellum and tarsi should be investigated for the potential to discover novel feeding deterrents of mosquito vectors.neuropeptide GPCR | sucrose taste | sensory neuron | chemical target validation | feeding deterrent

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confidence: 99%

Leucokinin mimetic elicits aversive behavior in mosquito Aedes aegypti (L.) and inhibits the sugar taste neuron

Kwon

Agha

Smith

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…It has been further postulated that a C‐terminal aldehyde moiety could form a covalent reversible Schiff base (imide linkage) with the amino group of a Lys residue 36 in an insect kinin receptor pocket, thereby modifying the ligand–receptor interaction characteristics of the resulting insect kinin analogue. Evaluations of two C‐terminal aldehyde kinin analogues, R‐LK‐CHO (Fmoc‐RFFPWG‐H) and V‐LK‐CHO (Boc‐VFFPWG‐H), in developmental and diuretic assays have been reported 9,37 . Both aldehyde analogues demonstrated in vitro stimulation of fluid secretion in isolated cricket Malpighian tubules in the physiological concentration range and matches the efficacy of the native achetakinins, thereby providing evidence that they could interact with an insect kinin receptor site.…”

Section: Introductionmentioning

confidence: 93%

“…In addition, the insect kinins have been implicated in the regulation of digestive enzyme release 6–8 . More recently, insect kinins, and/or analogues, have been reported to inhibit weight gain by larvae of the tobacco budworm Heliothis virescens and corn earworm Helicoverpa zea , 3,9,10 both serious agricultural pests.…”

Section: Introductionmentioning

confidence: 99%

“…Myotropic and diuretic assays of tissues in vitro as well as assays using stably expressed insect kinin receptors show that the full biological activity of the insect kinins resides in the C‐terminal pentapeptide, which is the active core, 5,9,11 with the exceptions of the housefly Malpighian tubule fluid secretion assay 12 and an expressed insect kinin receptor from the mosquito Aedes aegypti , where the C‐terminal pentapeptide core is less potent than native peptides by several orders of magnitude. Diuretic, myotropic, and/or receptor interaction activity in these assays is completely lost when the C‐terminal amide of the insect kinins is replaced with a negatively charged acid moiety 13,14 .…”

Section: Introductionmentioning

confidence: 99%

“…The graph at bottom illustrates the percent mortality observed in these H. zea larvae injected with either 500 pm or 5 nm of V‐LK‐CHO for 5 days compared with saline‐injected controls. This figure was reprinted from Nachman et al ., 9 with the permission of Elsevier Press.…”

Section: Introductionmentioning

confidence: 99%

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Toward the Development of Novel Pest Management Agents Based upon Insect Kinin Neuropeptide Analogues

Nachman

Pietrantonio

Coast

2009

Annals of the New York Academy of Sciences

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Insect kinin neuropeptides share a common C-terminal pentapeptide sequence Phe(1)-Xaa(1)(2)-Xaa(2)(3)-Trp(4)-Gly(5)-NH(2) (Xaa(1)(2)= His, Asn, Phe, Ser or Tyr; Xaa(2)(3)= Pro, Ser or Ala) and have been isolated from a number of insects. They have been associated with the regulation of such diverse processes as hindgut contraction, diuresis, and the release of digestive enzymes. In this review, the chemical, conformational, and stereochemical aspects of the activity of the insect kinins with expressed receptors and/or biological assays are reviewed. With this information, both nonselective and selective biostable analogues have been designed that protect peptidase-susceptible sites in the insect kinin sequence and demonstrate significant retention of activity in both receptor and biological assays. C-terminal aldehyde insect kinin analogues modify the activity of the insect kinins, leading to inhibition of weight gain and mortality in corn earworm larvae and selective inhibition of diuresis in the housefly. Promising mimetic analogue leads in the development of selective agents capable of disrupting insect kinin-regulated processes have been identified that may provide interesting tools for arthropod endocrinologists and new pest insect management strategies in the future.

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Comparative structure‐activity analysis of insect kinin core analogs on recombinant kinin receptors from Southern cattle tick Boophilus microplus (Acari: Ixodidae) and mosquito Aedes aegypti (Diptera: Culicidae)

Taneja-Bageshwar¹,

Strey²,

Zubrzak³

et al. 2006

Arch Insect Biochem Physiol

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The systematic analysis of structure-activity relationships of insect kinins on two heterologous receptor-expressing systems is described. Previously, kinin receptors from the southern cattle tick, Boophilus microplus (Canestrini), and the dengue vector, the mosquito Aedes aegypti (L.), were functionally and stably expressed in CHO-K1 cells. In order to determine which kinin residues are critical for the peptide-receptor interaction, kinin core analogs were synthesized as an Ala-replacement series of the peptide FFSWGa and tested by a calcium bioluminescence plate assay. The amino acids Phe(1) and Trp(4) were essential for activity of the insect kinins in both receptors. It was confirmed that the pentapeptide kinin core is the minimum sequence required for activity and that the C-terminal amide is also essential. In contrast to the tick receptor, a large increase in efficacy is observed in the mosquito receptor when the C-terminal pentapeptide is N-terminally extended to a hexapeptide. The aminoisobutyric acid (Aib)-containing analog, FF[Aib]WGa, was as active as superagonist FFFSWGa on the mosquito receptor in contrast to the tick receptor where it was statistically more active than FFFSWGa by an order of magnitude. This restricted conformation Aib analog provides information on the conformation associated with the interaction of the insect kinins with these two receptors. Furthermore, the analog FF[Aib]WGa has been previously shown to resist degradation by the peptidases ACE and nephrilysin and represents an important lead in the development of biostable insect kinin analogs that ticks and mosquitoes cannot readily deactivate.

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A C-terminal aldehyde insect kinin analog enhances inhibition of weight gain and induces significant mortality in Helicoverpa zea larvae

Cited by 34 publications

References 25 publications

Leucokinin mimetic elicits aversive behavior in mosquito Aedes aegypti (L.) and inhibits the sugar taste neuron

Leucokinin mimetic elicits aversive behavior in mosquito Aedes aegypti (L.) and inhibits the sugar taste neuron

Toward the Development of Novel Pest Management Agents Based upon Insect Kinin Neuropeptide Analogues

Comparative structure‐activity analysis of insect kinin core analogs on recombinant kinin receptors from Southern cattle tick Boophilus microplus (Acari: Ixodidae) and mosquito Aedes aegypti (Diptera: Culicidae)

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