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From Synthetic Fragments of Endogenous Three-Finger Proteins to Potential Drugs

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dc.contributor.authorKryukova, Elena V.
dc.contributor.authorEgorova, Natalia S.
dc.contributor.authorKudryavtsev, DenisS.
dc.contributor.authorLebedev, Dmitry S.
dc.contributor.authorTsetlin, Victor I.
dc.date.accessioned2024-11-21T10:03:10Z
dc.date.available2024-11-21T10:03:10Z
dc.date.issued2019
dc.description.abstractThe proteins of the Ly6 family have a three-finger folding as snake venom alpha-neurotoxins, targeting nicotinic acetylcholine receptors (nAChRs), and some of them, like mammalian secreted Ly6/ uPAR protein (SLURP1) and membrane-attached Ly-6/ neurotoxin (Lynx1), also interact with distinct nAChR subtypes. We believed that synthetic fragments of these endogenous proteins might open new ways for drug design because nAChRs are well-known targets for developing analgesics and drugs against neurodegenerative diseases. Since interaction with nAChRs was earlier shown for synthetic fragments of the alpha-neurotoxin central loop II, we synthesized a 15-membered fragment of human Lynx1, its form with two Cys residues added at the N- and C-termini and forming a disulfide, as well as similar forms of human SLURP1, SLURP2, and of Drosophila sleepless protein (SSS). The IC50 values measured in competition with radioiodinated alpha-bungarotoxin for binding to the membrane-bound Torpedo californica nAChR were 4.9 and 7.4 mu M for Lynx1 and SSS fragments, but over 300 mu M for SLURP1 or SLURP2 fragments. The affinity of these compounds for the alpha 7 nAChR in the rat pituitary tumor-derived cell line GH4C1 was different: 13.1 and 147 mu M for SSS and Lynx1 fragments, respectively. In competition for the ligand-binding domain of the alpha 9 nAChR subunit, SSS and Lynx1 fragments had IC50 values of about 40 mu M, which correlates with the value found for the latter with the rat alpha 9 alpha 10 nAChR expressed in the Xenopus oocytes. Thus, the activity of these synthetic peptides against muscle-type and alpha 9 alpha 10 nAChRs indicates that they may be useful in design of novel myorelaxants and analgesics.
dc.identifier.citationFrom Synthetic Fragments of Endogenous Three-Finger Proteins to Potential Drugs / Kryukova, ElenaV [et al.] // Frontiers in Pharmacology. - 2019. - 10. - 10.3389/fphar.2019.00748
dc.identifier.doi10.3389/fphar.2019.00748
dc.identifier.urihttps://www.doi.org/10.3389/fphar.2019.00748
dc.identifier.urihttps://www.scopus.com/record/display.uri?eid=2-s2.0-85080865831&origin=resultslist
dc.identifier.urihttp://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=Alerting&SrcApp=Alerting&DestApp=WOS_CPL&DestLinkType=FullRecord&UT=WOS:000473658300001
dc.identifier.urihttps://openrepository.mephi.ru/handle/123456789/18354
dc.relation.ispartofFrontiers in Pharmacology
dc.titleFrom Synthetic Fragments of Endogenous Three-Finger Proteins to Potential Drugs
dc.typeArticle
dspace.entity.typePublication
oaire.citation.volume10
relation.isOrgUnitOfPublicationc8407a6f-7272-450d-8d99-032352c76b55
relation.isOrgUnitOfPublication.latestForDiscoveryc8407a6f-7272-450d-8d99-032352c76b55
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