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

Файлы
W2955288167.pdf(3.6 MB)
Дата
2019
Авторы
Kryukova, Elena V.
Egorova, Natalia S.
Kudryavtsev, DenisS.
Lebedev, Dmitry S.
Tsetlin, Victor I.
Journal Title
Journal ISSN
Volume Title
Издатель
Научные группы
Организационные подразделения
OrgUnit Logo
Организационная единица
Инженерно-физический институт биомедицины
Цель ИФИБ и стратегия развития – это подготовка высококвалифицированных кадров на базе передовых исследований и разработок новых перспективных методов и материалов в области инженерно-физической биомедицины. Занятие лидерских позиций в биомедицинских технологиях XXI века и внедрение их в образовательный процесс, что отвечает решению практикоориентированной задачи мирового уровня – диагностике и терапии на клеточном уровне социально-значимых заболеваний человека.
Выпуск журнала
Аннотация
The 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.
Описание
Ключевые слова
Цитирование
From Synthetic Fragments of Endogenous Three-Finger Proteins to Potential Drugs / Kryukova, ElenaV [et al.] // Frontiers in Pharmacology. - 2019. - 10. - 10.3389/fphar.2019.00748
URI
https://www.doi.org/10.3389/fphar.2019.00748
 https://www.scopus.com/record/display.uri?eid=2-s2.0-85080865831&origin=resultslist
 http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=Alerting&SrcApp=Alerting&DestApp=WOS_CPL&DestLinkType=FullRecord&UT=WOS:000473658300001
 https://openrepository.mephi.ru/handle/123456789/18354
Коллекции
Публикации