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Hexapeptides from mammalian inhibitory hormone hunt 3 activate and inactivate nematode reproduction : Bioactive peptides. / Hart, John E.; Mohan, Sharad; Davies, Keith; Ferneyhough, Ben ; Clarke, Iain; Hunt, John; Shnyder, Steve; Mundy, Christopher; Copsey, David ; Howlett, David; Newton, Russell.

In: BioRxiv, 30.09.2021.

Research output: Contribution to journalArticle

Harvard

Hart, JE, Mohan, S, Davies, K, Ferneyhough, B, Clarke, I, Hunt, J, Shnyder, S, Mundy, C, Copsey, D, Howlett, D & Newton, R 2021, 'Hexapeptides from mammalian inhibitory hormone hunt 3 activate and inactivate nematode reproduction: Bioactive peptides', BioRxiv. https://doi.org/10.1101/2021.09.28.462091

APA

Hart, J. E., Mohan, S., Davies, K., Ferneyhough, B., Clarke, I., Hunt, J., Shnyder, S., Mundy, C., Copsey, D., Howlett, D., & Newton, R. (2021). Hexapeptides from mammalian inhibitory hormone hunt 3 activate and inactivate nematode reproduction: Bioactive peptides. BioRxiv. https://doi.org/10.1101/2021.09.28.462091

Vancouver

Author

Hart, John E. ; Mohan, Sharad ; Davies, Keith ; Ferneyhough, Ben ; Clarke, Iain ; Hunt, John ; Shnyder, Steve ; Mundy, Christopher ; Copsey, David ; Howlett, David ; Newton, Russell. / Hexapeptides from mammalian inhibitory hormone hunt 3 activate and inactivate nematode reproduction : Bioactive peptides. In: BioRxiv. 2021.

Bibtex

@article{ffed28753bb24b4db63867a616ccc1aa,
title = "Hexapeptides from mammalian inhibitory hormone hunt 3 activate and inactivate nematode reproduction: Bioactive peptides",
abstract = "Increased reproduction (x3) of the entomopathogenic nematode Steinernema siamkayai occurred when exposed to one synthetic peptide (IEPVFT), while the fecundity of worms exposed to hexamer (KLKMNG) was reduced (x0.5). These hexamers were opposite ends of a 14 amino acid (aa) synthetic peptide KLKMNGKNIEPVFT (EPL030). The bioactivity of the hexamers is surprising it is a scrambled-sequence control of another peptide, MKPLTGKVKEFNNI (EPL001) which are bioinformatically obscure. EPL001 emerged from a physicochemical fractionation aimed at finding a postulated hormone that is reproductively related and tissue-mass reducing and has antiproliferative effects on human prostate cancer cells and rat bone marrow cells in vitro. Intracerebroventricular infusion of EPL001 in sheep was associated with elevated growth hormone in peripheral blood and reduced prolactin. The highly dissimilar EPL001 and EPL030 nonetheless have the foregoing biological effects in common in mammalian systems, while being divergently pro- and anti-fecundity respectively in the nematode Caenorhabditis elegans. Immunoprecipitation of EPL001 using an anti-EPL001 antibody suggests it encodes the sheep neuroendocrine prohormone secretogranin II (sSgII). Using bespoke bioinformatics with six sSgII residues deduced bioactivity to key aa: MKPLTGKVKEFNNI. Peptides more potent as cell inhibitors than EPL001 suggest a stereospecific bimodular tri-residue signature (i.e. simultaneous accessibility for binding of two specific trios of aa side chains, MKP & VFN). An evolutionarily conserved receptor is conceptualised as having dimeric binding sites, each with ligand-matching bimodular stereocentres. Sequence analysis and computational modelling suggest the activity of the control peptide EPL030 and its N- and C-terminal hexapeptide progeny is due the novel hormonal motif MKPVFN.",
keywords = "NEMATODE, Peptide mimetics, Structure-activity relationships, Secretogranin II, Scrambled peptides, Antiproliferative effects, Prostate cancer cells (PC3), Bone Marrow Cells, Pituitery hormone",
author = "Hart, {John E.} and Sharad Mohan and Keith Davies and Ben Ferneyhough and Iain Clarke and John Hunt and Steve Shnyder and Christopher Mundy and David Copsey and David Howlett and Russell Newton",
year = "2021",
month = sep,
day = "30",
doi = "10.1101/2021.09.28.462091",
language = "English",
journal = "BioRxiv",

}

RIS

TY - JOUR

T1 - Hexapeptides from mammalian inhibitory hormone hunt 3 activate and inactivate nematode reproduction

T2 - Bioactive peptides

AU - Hart, John E.

AU - Mohan, Sharad

AU - Davies, Keith

AU - Ferneyhough, Ben

AU - Clarke, Iain

AU - Hunt, John

AU - Shnyder, Steve

AU - Mundy, Christopher

AU - Copsey, David

AU - Howlett, David

AU - Newton, Russell

PY - 2021/9/30

Y1 - 2021/9/30

N2 - Increased reproduction (x3) of the entomopathogenic nematode Steinernema siamkayai occurred when exposed to one synthetic peptide (IEPVFT), while the fecundity of worms exposed to hexamer (KLKMNG) was reduced (x0.5). These hexamers were opposite ends of a 14 amino acid (aa) synthetic peptide KLKMNGKNIEPVFT (EPL030). The bioactivity of the hexamers is surprising it is a scrambled-sequence control of another peptide, MKPLTGKVKEFNNI (EPL001) which are bioinformatically obscure. EPL001 emerged from a physicochemical fractionation aimed at finding a postulated hormone that is reproductively related and tissue-mass reducing and has antiproliferative effects on human prostate cancer cells and rat bone marrow cells in vitro. Intracerebroventricular infusion of EPL001 in sheep was associated with elevated growth hormone in peripheral blood and reduced prolactin. The highly dissimilar EPL001 and EPL030 nonetheless have the foregoing biological effects in common in mammalian systems, while being divergently pro- and anti-fecundity respectively in the nematode Caenorhabditis elegans. Immunoprecipitation of EPL001 using an anti-EPL001 antibody suggests it encodes the sheep neuroendocrine prohormone secretogranin II (sSgII). Using bespoke bioinformatics with six sSgII residues deduced bioactivity to key aa: MKPLTGKVKEFNNI. Peptides more potent as cell inhibitors than EPL001 suggest a stereospecific bimodular tri-residue signature (i.e. simultaneous accessibility for binding of two specific trios of aa side chains, MKP & VFN). An evolutionarily conserved receptor is conceptualised as having dimeric binding sites, each with ligand-matching bimodular stereocentres. Sequence analysis and computational modelling suggest the activity of the control peptide EPL030 and its N- and C-terminal hexapeptide progeny is due the novel hormonal motif MKPVFN.

AB - Increased reproduction (x3) of the entomopathogenic nematode Steinernema siamkayai occurred when exposed to one synthetic peptide (IEPVFT), while the fecundity of worms exposed to hexamer (KLKMNG) was reduced (x0.5). These hexamers were opposite ends of a 14 amino acid (aa) synthetic peptide KLKMNGKNIEPVFT (EPL030). The bioactivity of the hexamers is surprising it is a scrambled-sequence control of another peptide, MKPLTGKVKEFNNI (EPL001) which are bioinformatically obscure. EPL001 emerged from a physicochemical fractionation aimed at finding a postulated hormone that is reproductively related and tissue-mass reducing and has antiproliferative effects on human prostate cancer cells and rat bone marrow cells in vitro. Intracerebroventricular infusion of EPL001 in sheep was associated with elevated growth hormone in peripheral blood and reduced prolactin. The highly dissimilar EPL001 and EPL030 nonetheless have the foregoing biological effects in common in mammalian systems, while being divergently pro- and anti-fecundity respectively in the nematode Caenorhabditis elegans. Immunoprecipitation of EPL001 using an anti-EPL001 antibody suggests it encodes the sheep neuroendocrine prohormone secretogranin II (sSgII). Using bespoke bioinformatics with six sSgII residues deduced bioactivity to key aa: MKPLTGKVKEFNNI. Peptides more potent as cell inhibitors than EPL001 suggest a stereospecific bimodular tri-residue signature (i.e. simultaneous accessibility for binding of two specific trios of aa side chains, MKP & VFN). An evolutionarily conserved receptor is conceptualised as having dimeric binding sites, each with ligand-matching bimodular stereocentres. Sequence analysis and computational modelling suggest the activity of the control peptide EPL030 and its N- and C-terminal hexapeptide progeny is due the novel hormonal motif MKPVFN.

KW - NEMATODE

KW - Peptide mimetics

KW - Structure-activity relationships

KW - Secretogranin II

KW - Scrambled peptides

KW - Antiproliferative effects

KW - Prostate cancer cells (PC3)

KW - Bone Marrow Cells

KW - Pituitery hormone

U2 - 10.1101/2021.09.28.462091

DO - 10.1101/2021.09.28.462091

M3 - Article

JO - BioRxiv

JF - BioRxiv

ER -