Enhanced in vivo activity of peptidase-resistant analogs of the insect kinin neuropeptide family

Nachman, Ronald J.; Strey, Allison; Isaac, Elwyn; Pryor, Nan W.; López, J. D.; Deng, Jin; Coast, Geoffrey M.

doi:10.1016/s0196-9781(01)00654-4

Cited by 81 publications

(79 citation statements)

References 22 publications

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“…Although both the Aib-containing analogs 1728 and 1729 elicit hindgut contractions in Rhodnius; 1728 is more potent (39). Structural modifications of insect kinins, such as the incorporation of Aib and β-amino acids with an additional methylene group (-CH 2 -), render these peptides biostable, because they are protease resistant (8,(10)(11)(12)26). Our hypothesis is that the potent analog 1728 enters the labellar and tarsal sensilla (30) and diffuses through the aqueous sensillum lymph to activate the Aedae-KR expressed in sucrose taste neurons, thereby decreasing sucrose taste perception.…”

Section: Discussionmentioning

confidence: 99%

“…We verified that the aedeskinins activate the single Aedes kinin receptor (Aedae-KR), a G protein-coupled receptor (GPCR) that signals through intracellular calcium (9). We designed kinin analogs to be resistant to degrading peptidases and therefore exhibit sustained high potency (10,11). One biostable kinin peptidomimetic containing aminoisobutyric acid, 1728, has potency similar to or higher than the aedeskinins on recombinant receptors (12).…”

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confidence: 95%

“…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%

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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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Section: Discussionmentioning

confidence: 99%

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confidence: 95%

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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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“…The natural members of the pyrokinin/PBAN family, truncated PBAN fragments, and the PBAN C-terminal hexapeptide Ala-series of analogs listed in Fig. 4 were synthesized by the solid-phase method on an ABI 433A Peptide Synthesizer with modified FastMoc0.25 procedure (0.25mM scale, prolonged double coupling), using the Fmoc-strategy, HPLC purified and quantified via amino acid analysis as previously described [20].…”

Section: Cho Cell Expressionmentioning

confidence: 99%

The pheromone biosynthesis activating neuropeptide (PBAN) receptor of Heliothis virescens: Identification, functional expression, and structure–activity relationships of ligand analogs

et al. 2008

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Pheromone biosynthesis activating neuropeptide (PBAN) promotes synthesis and release of sex pheromones in moths. We have identified and functionally expressed a PBAN receptor from Heliothis virescens (HevPBANR) and elucidated structure-activity relationships of PBAN analogs. Screening of a larval CNS cDNA library revealed three putative receptor subtypes and nucleotide sequence comparisons suggest they are produced through alternative splicing at the 3'-end. RT-PCR amplified preferentially HevPBANR-C from female pheromone glands. CHO cells expressing HevPBANR-C are highly sensitive to PBAN and related analogs, especially those sharing the C-terminal pentapeptide core, FXPRLamide (X = T, S or V). Alanine replacements in the C-terminal hexapeptide (YFTPRLamide) revealed the relative importance of each residue in the active core as follows, R 5 >L 6 >F 2 ≫P 4 >T 3 ≫Y 1 . This study provides a framework for the rational design of PBANR-specific agonists and/or antagonists that could be exploited for disruption of reproductive function in agriculturally important insect pests.

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“…Accordingly, the principal neurohaemal organ of insects, the corpus cardiacum, is often expected to liberate dozens of different peptidic neurohormones, which ought to be quickly destroyed or inactivated by aminopeptidase enzymes of the haemolymph (cf. Quistad et al, 1984;Predel, 2001;Schoofs et al, 2001;Nachman et al, 2002;Audsley & Weaver, 2003;Roller et al, 2003). Professional biologists are astonished by the enormous progress in chemical synthesis and methods of peptide analysis.…”

Section: Discussionmentioning

confidence: 99%

The effect of corazonin on heartbeat reversal in pupae of the tobacco hornworm, Manduca sexta (Lepidoptera: Sphingidae)

Sláma¹

2004

Eur. J. Entomol.

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Abstract. Heartbeat reversal patterns have been monitored in the body of diapausing pupae of M. sexta 2 h before and 3 h after the injections of [Arg 7 ]-corazonin, using noninvasive thermographic and optocardiographic methods. Large dosages (10 -6 M final concentrations of corazonin in the body) caused almost immediate, adrenaline-like enhancement of the anterograde heartbeat. During the relatively short, acute phase of the tachycardia induced by corazonin, the systolic anterograde contractions of the heart increased in average from 10.5 to 24 pulses per min, culminating at 2.5 min after the injections. Duration of the acute period of tachycardia was only 7 to 20 min, which was followed by a period of slightly elevated, residual anterograde heartbeat which persisted occasionally for 1 to 3 h. Smaller dosages of corazonin (10 -7 M concentrations in the body) occasionally also produced a less intensive cardiotropic effect, while the more diluted samples were completely inactive. In pupae of the beetle T. molitor, injections of corazonin (10 -6 M in the body) had no effect on the rate of in vivo heartbeat at all. Pharmacological analysis of the effects of corazonin in M. sexta indicated that the cardiostimulating effects of corazonin did not conform with the expected action of a peptidic neurohormone. A possibility that these effects might be artifacts produced by the low molecular breakdown products of corazonin has been discussed.

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Enhanced in vivo activity of peptidase-resistant analogs of the insect kinin neuropeptide family

Cited by 81 publications

References 22 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

The pheromone biosynthesis activating neuropeptide (PBAN) receptor of Heliothis virescens: Identification, functional expression, and structure–activity relationships of ligand analogs

The effect of corazonin on heartbeat reversal in pupae of the tobacco hornworm, Manduca sexta (Lepidoptera: Sphingidae)

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