Somatostatin Venom Analogs Evolved by Fish-hunting Cone Snails: From Prey Capture Behavior to Identifying Drug Leads

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2022 Mar 23

PMID 35319982

Authors

Iris Bea L Ramiro

Walden E Bjorn-Yoshimoto

Julita S Imperial

Joanna Gajewiak

Paula Florez Salcedo

Maren Watkins

Dylan Taylor

William Resager

Beatrix Ueberheide

Hans Brauner-Osborne

Frank G Whitby

Christopher P Hill

Laurent F Martin

Amol Patwardhan

Gisela P Concepcion

Baldomero M Olivera

Helena Safavi-Hemami

Affiliations

Soon will be listed here.

Abstract

Somatostatin (SS) is a peptide hormone with diverse physiological roles. By investigating a deep-water clade of fish-hunting cone snails, we show that predator-prey evolution has generated a diverse set of SS analogs, each optimized to elicit specific systemic physiological effects in prey. The increased metabolic stability, distinct SS receptor activation profiles, and chemical diversity of the venom analogs make them suitable leads for therapeutic application, including pain, cancer, and endocrine disorders. Our findings not only establish the existence of SS-like peptides in animal venoms but also serve as a model for the synergy gained from combining molecular phylogenetics and behavioral observations to optimize the discovery of natural products with biomedical potential.

Citing Articles

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References

Zhang Y, Alfonso Yanez Guerra L, Egertova M, Zampronio C, Jones A, Elphick M . Molecular and functional characterization of somatostatin-type signalling in a deuterostome invertebrate. Open Biol. 2020; 10(9):200172. PMC: 7536072. DOI: 10.1098/rsob.200172. View

Craig A, Norberg T, Griffin D, Hoeger C, Akhtar M, Schmidt K . Contulakin-G, an O-glycosylated invertebrate neurotensin. J Biol Chem. 1999; 274(20):13752-9. DOI: 10.1074/jbc.274.20.13752. View

TABER R . Predictive value of analgesic assays in mice and rats. Adv Biochem Psychopharmacol. 1973; 8(0):191-211. View

Chaplan S, Bach F, Pogrel J, Chung J, Yaksh T . Quantitative assessment of tactile allodynia in the rat paw. J Neurosci Methods. 1994; 53(1):55-63. DOI: 10.1016/0165-0270(94)90144-9. View

Dereeper A, Guignon V, Blanc G, Audic S, Buffet S, Chevenet F . Phylogeny.fr: robust phylogenetic analysis for the non-specialist. Nucleic Acids Res. 2008; 36(Web Server issue):W465-9. PMC: 2447785. DOI: 10.1093/nar/gkn180. View

Motomura M, Johnston I, Lang B, Vincent A, Newsom-Davis J . An improved diagnostic assay for Lambert-Eaton myasthenic syndrome. J Neurol Neurosurg Psychiatry. 1995; 58(1):85-7. PMC: 1073275. DOI: 10.1136/jnnp.58.1.85. View

Emsley P, Lohkamp B, Scott W, Cowtan K . Features and development of Coot. Acta Crystallogr D Biol Crystallogr. 2010; 66(Pt 4):486-501. PMC: 2852313. DOI: 10.1107/S0907444910007493. View

Richter K, Sagawe S, Hecker A, Kullmar M, Askevold I, Damm J . C-Reactive Protein Stimulates Nicotinic Acetylcholine Receptors to Control ATP-Mediated Monocytic Inflammasome Activation. Front Immunol. 2018; 9:1604. PMC: 6077200. DOI: 10.3389/fimmu.2018.01604. View

Kabsch W . XDS. Acta Crystallogr D Biol Crystallogr. 2010; 66(Pt 2):125-32. PMC: 2815665. DOI: 10.1107/S0907444909047337. View

10.

Szolcsanyi J, Bolcskei K, Szabo A, Pinter E, Petho G, Elekes K . Analgesic effect of TT-232, a heptapeptide somatostatin analogue, in acute pain models of the rat and the mouse and in streptozotocin-induced diabetic mechanical allodynia. Eur J Pharmacol. 2004; 498(1-3):103-9. DOI: 10.1016/j.ejphar.2004.07.085. View

11.

Brennan T, Zahn P, Pogatzki-Zahn E . Mechanisms of incisional pain. Anesthesiol Clin North Am. 2005; 23(1):1-20. DOI: 10.1016/j.atc.2004.11.009. View

12.

Gorlin A, Rosenfeld D, Maloney J, Wie C, McGarvey J, Trentman T . Survey of pain specialists regarding conversion of high-dose intravenous to neuraxial opioids. J Pain Res. 2016; 9:693-700. PMC: 5036565. DOI: 10.2147/JPR.S113216. View

13.

Shenoy P, Kuo A, Khan N, Gorham L, Nicholson J, Corradini L . The Somatostatin Receptor-4 Agonist J-2156 Alleviates Mechanical Hypersensitivity in a Rat Model of Breast Cancer Induced Bone Pain. Front Pharmacol. 2018; 9:495. PMC: 5962878. DOI: 10.3389/fphar.2018.00495. View

14.

Williams C, Headd J, Moriarty N, Prisant M, Videau L, Deis L . MolProbity: More and better reference data for improved all-atom structure validation. Protein Sci. 2017; 27(1):293-315. PMC: 5734394. DOI: 10.1002/pro.3330. View

15.

King G . Venoms as a platform for human drugs: translating toxins into therapeutics. Expert Opin Biol Ther. 2011; 11(11):1469-84. DOI: 10.1517/14712598.2011.621940. View

16.

Winn M, Ballard C, Cowtan K, Dodson E, Emsley P, Evans P . Overview of the CCP4 suite and current developments. Acta Crystallogr D Biol Crystallogr. 2011; 67(Pt 4):235-42. PMC: 3069738. DOI: 10.1107/S0907444910045749. View

17.

Yarotskyy V, Elmslie K . omega-conotoxin GVIA alters gating charge movement of N-type (CaV2.2) calcium channels. J Neurophysiol. 2008; 101(1):332-40. DOI: 10.1152/jn.91064.2008. View

18.

Allen J, Hofer K, McCumber D, Wagstaff J, Layer R, McCabe R . An assessment of the antinociceptive efficacy of intrathecal and epidural contulakin-G in rats and dogs. Anesth Analg. 2007; 104(6):1505-13, table of contents. DOI: 10.1213/01.ANE.0000219586.65112.FA. View

19.

Weissburg M . The fluid dynamical context of chemosensory behavior. Biol Bull. 2000; 198(2):188-202. DOI: 10.2307/1542523. View

20.

Imperial J, Chen P, Sporning A, Terlau H, Daly N, Craik D . Tyrosine-rich conopeptides affect voltage-gated K+ channels. J Biol Chem. 2008; 283(34):23026-32. PMC: 2517004. DOI: 10.1074/jbc.M800084200. View