An amphiphilic, PK/PBAN analog is a selective pheromonotropic antagonist that penetrates the cuticle of a heliothine insect

Nachman, Ronald J.; Teal, Peter E. A.; Aziz, Orna Ben; Davidovitch, Michael; Zubrzak, Paweł; Altstein, Miriam

doi:10.1016/j.peptides.2008.09.024

Cited by 22 publications

(15 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The use of neuropeptidergic systems as targets for pest insect control has been a widely accepted concept and is practiced in limited cases [19, 26, 27, 29, 37, 41]. Peptidomimetics that increase stability and bioavailability have been studied for their use in pest control.…”

Section: Resultsmentioning

confidence: 99%

“…For example, a beta-amino acid pyrokinin analog (Ac-Y[β 3 F]TPRLamide) accelerates pupariation in the flesh fly S. bullata at a similar potency (0.2 pmol/larva) to the native pyrokinin, while it induces irregular pupariation behavior patterns at higher concentrations, which indicates potential neurotoxic properties [29]. A linear PK/PBAN antagonist lead (RYF[dF]PRLa) was reported as a potent inhibitor of sex pheromone biosynthesis in Heliothis peltigera , and an analog of this lead sequence containing an appended hydrophobic group on the N-terminus demonstrates an ability to penetrate the cuticle of a heliothine insect [27]. Pupal diapause of H. zea can be disrupted using DH agonistic and/or antagonistic peptidomimetics [17, 41], and biostable analogs of the insectatachykinin, insect kinin, and pyrokinin families show aphicidal activity that match or exceed the activity of some commercially available aphicides [37].…”

Section: Resultsmentioning

confidence: 99%

“…All pyrokinin analogs and peptide mimetics were synthesized as described previously by Nachman et al [24, 25, 27, 28]. Peptides from T. castaneum were purchased from Genescript (Piscataway, NJ).…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Functional characterization of five different PRXamide receptors of the red flour beetle Tribolium castaneum with peptidomimetics and identification of agonists and antagonists

et al. 2015

Self Cite

View full text Add to dashboard Cite

The neuropeptidergic system in insects is an excellent target for pest control strategies. One promising biorational approach is the use of peptidomimetics modified from endogenous ligands to enhance biostability and bioavailability. In this study, we functionally characterized five different G protein-coupled receptors in a phylogenetic cluster, containing receptors for PRXamide in the red flour beetle Tribolium castaneum, by evaluating a series of 70 different peptides and peptidomimetics. Three pyrokinin receptors (TcPKr-A, -B, and –C), cardioacceleratory peptide receptor (TcCAPAr) and ecdysis triggering hormone receptor (TcETHr) were included in the study. Strong agonistic or antagonistic peptidomimetics were identified, and included beta-proline (β3P) modification of the core amino acid residue proline and also a cyclo-peptide. It is common for a ligand to act on multiple receptors. In a number of cases, a ligand acting as an agonist on one receptor was an efficient antagonist on another receptor, suggesting complex outcomes of a peptidomimetic in a biological system. Interestingly, TcPK-A was highly promiscuous with a high number of agonists, while TcPK-C and TcCAPAr had a lower number of agonists, but a higher number of compounds acting as an antagonist. This observation suggests that a target GPCR with more promiscuity will provide better success for peptidomimetic approaches. This study is the first description of peptidomimetics on a CAPA receptor and resulted in the identification of peptidomimetic analogs that demonstrate antagonism of CAPA ligands. The PRXamide receptor assays with peptidomimetics provide useful insights into the biochemical properties of receptors.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Functional characterization of five different PRXamide receptors of the red flour beetle Tribolium castaneum with peptidomimetics and identification of agonists and antagonists

et al. 2015

Self Cite

View full text Add to dashboard Cite

show abstract

“…37 A PK/ PBAN antagonist lead (RYF[dF]PRLa) was reported as a potent inhibitor of a sex pheromone biosynthesis in Heliothis peltigera. 38 Using a diapause hormone (DH) agonistic and/or antagonistic peptidomimetics the pupal diapause of Helicoverpa zea was disrupted 39 and analogs of the pyrokinin, insect kinin and insect tachykinin families showed aphicidal activity, that was better than some commercially available aphicides. …”

Section: Discussionmentioning

confidence: 99%

Ecdysis-related pleiotropic neuropeptides expression during Anopheles albimanus development

et al. 2017

View full text Add to dashboard Cite

“…The primary method utilized previously to develop antagonists to the pyrokinin/PBAN family was to use a D-Phe substitution (17,18), such as found in the PBAN antagonist PPK-AA (18). Another method for antagonist development is to incorporate β-amino acids (16,19), but our preliminary data evaluation showed that neither PPK-AA nor other compounds containing either D-Phe or both D-Phe and β-amino acids could effectively inhibit DH activity in our diapause termination assay.…”

Section: Preventing Pupal Diapause With Dh Agonists Administered To Lmentioning

confidence: 99%

Disruption of insect diapause using agonists and an antagonist of diapause hormone

Zhang

Nachman

Kaczmarek

et al. 2011

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

Self Cite

View full text Add to dashboard Cite

The dormant state known as diapause is widely exploited by insects to circumvent winter and other adverse seasons. For an insect to survive, feed, and reproduce at the appropriate time of year requires fine coordination of the timing of entry into and exit from diapause. One of the hormones that regulates diapause in moths is the 24-aa neuropeptide, diapause hormone (DH). Among members of the Helicoverpa/Heliothis complex of agricultural pests, DH prompts the termination of pupal diapause. Based on the structure of DH, we designed several agonists that are much more active than DH in breaking diapause. One such agonist that we describe also prevents the entry into pupal diapause when administered to larvae that are environmentally programmed for diapause. In addition, we used the unique antagonist development strategy of incorporating a dihydroimidazole ("Jones") trans-Proline mimetic motif into one of our DH agonists, thereby converting the agonist into a DH antagonist that blocks the termination of diapause. These results suggest potential for using such agents or next-generation derivatives for derailing the success of overwintering in pest species.diapause manipulation | peptidomimetics C oordinating active phases of the life cycle with seasons that provide food resources and suitable environmental conditions is crucial for sustaining viable insect populations. Major portions of the year, most notably winters in temperate zones, are unsuitable for continuous development, and most insects have evolved periods of dormancy (diapause), characterized by suppressed metabolism and bolstered stress responses that enhance survival during unfavorable seasons. Short day lengths of late summer commonly trigger the onset of diapause (1, 2), and these environmental signals prompt endocrine responses that directly initiate and eventually terminate the diapause state (3).Desynchronizing an insect pest with its appropriate seasonal diapause could be used as a tool for disrupting pest populations (4). Altering the timing of diapause has the potential to evoke ecological suicide if the insect is forced to be active during a time of year when climatic conditions are adverse or food resources are absent. Blocking entry into diapause in the autumn, breaking out of an overwintering diapause prematurely, or failing to terminate diapause at the appropriate time in the spring all have potential for desynchronizing the temporal distribution of insects. We report here the development of unique agents capable of disrupting the overwintering pupal diapause of the corn earworm, Helicoverpa zea, a member of the Heliothis/Helicoverpa complex, a worldwide group of noteworthy crop pests (5).Our target is diapause hormone (DH). This 24-aa neuropeptide, a pyrokinin in the DH-pheromone biosynthesis activating neuropeptide (PBAN) family, is best known for its action in initiating embryonic diapause in the commercial silkworm, Bombyx mori (6); however, recently, DH was also shown to exert an opposite effect in pupae of the Heliothis/Helicoverpa co...

show abstract

An amphiphilic, PK/PBAN analog is a selective pheromonotropic antagonist that penetrates the cuticle of a heliothine insect

Cited by 22 publications

References 31 publications

Functional characterization of five different PRXamide receptors of the red flour beetle Tribolium castaneum with peptidomimetics and identification of agonists and antagonists

Functional characterization of five different PRXamide receptors of the red flour beetle Tribolium castaneum with peptidomimetics and identification of agonists and antagonists

Ecdysis-related pleiotropic neuropeptides expression during Anopheles albimanus development

Disruption of insect diapause using agonists and an antagonist of diapause hormone

Contact Info

Product

Resources

About