Vestnik of the Far East Branch of the Russian Academy of SciencesVestnik of the Far East Branch of the Russian Academy of SciencesВестник Дальневосточного отделения Российской академии наук0869-7698The Russian Academy of Sciences67606710.31857/S0869769824030064ISGGZEChemical Sciences. Bioorganic chemistryХимические науки. Биоорганическая химияReview ArticleLaboratory of Peptide Chemistry, G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of the Russian Academy of Sciences: forty years of research on peptides and proteins of sea anemonesЛаборатория химии пептидов Тихоокеанского института биоорганической химии ДВО РАН им. Г.Б. Елякова: сорок лет исследований пептидов и белков морских анемонhttps://orcid.org/0000-0003-3157-0930MonastyrnayaMargarita M.МонастырнаяМаргарита Михайловна
Russian Federation

Doctor of Chemical Sciences, Leading Researcher

доктор химических наук, ведущий научный сотрудник

rita1950@mail.ruhttps://orcid.org/0000-0002-8110-0382KozlovskayaEmma P.КозловскаяЭмма Павловна
Russian Federation

Doctor of Chemical Sciences, Chief Researcher, Professor

доктор химических наук, главный научный сотрудник, профессор

kozempa@mail.ruG.B. Elyakov Pacific Institute of Bioorganic Chemistry, FEB RASТихоокеанский институт биоорганической химии ДВО РАН им. Г.Б. Елякова15062024310112028022025Copyright ©; 2024, Russian Academy of SciencesCopyright ©; 2024, Российская академия наук2024Russian Academy of SciencesРоссийская академия наукhttps://journals.eco-vector.com/0869-7698/article/view/676067

The review briefly describes a research carried out over the past 40 years at the Laboratory of Peptide Chemistry of G.B. Elyakov Pacific Institute of Bioorganic Chemistry, FEB RAS (LPCh of PIBOC FEB RAS), in collaboration with Russian and foreign colleagues. The results of search, identification, and study of the structure, the biological activity, and the mechanisms of an interaction with the biological targets of peptides and polypeptides produced by the tropical sea anemone Heteractis crispa (=Heteractis magnifica, formerly Radianthus macrodactylus) are discussed. One of the main achievements of LPCh over the past years is the discovery of new structural type 2 neurotoxins, namely, six toxins that were not identified among the representatives of so-called long anemonotoxins in the first decade of foreign research (70–80s of the last century), and among them the first, previously unknown, double-chain neurotoxin. In addition, the presence of several multigene families expressing α-pore-forming toxins (actinoporins), serine protease inhibitors (Kunitz-type peptides), and APETx-like peptides forming the combinatorial libraries of the several dozen of highly homologous family members has been established. Using in silico methods (homologous modeling, alanine mutagenesis, full-atom molecular dynamics (MD) simulation), the spatial structures of the studied peptides and complexes with biological targets were predicted for the first time, and their structure-functional relationships were analyzed. This was the foundation for the further production of recombinant and mutant analogues on the basis of the combinatorial libraries for the purpose of conducting the electrophysiological studies of the mechanisms of their molecular interaction with targets as well as determining the pharmacological potential. In the review the most important results of recent years are presented. They are related to the discovery of analgesic, anti-inflammatory, and antitumor activity in a number of the studied peptides.

В обзоре кратко описаны исследования, проводившиеся в течение последних 40 лет в лаборатории химии пептидов Тихоокеанского института биоорганической химии ДВО РАН (ЛХП ТИБОХ ДВО РАН) в сотрудничестве с российскими и зарубежными коллегами. Обсуждаются результаты поиска, идентификации и изучения структуры, биологической активности и механизмов взаимодействия с биологическими мишенями пептидов и полипептидов, продуцируемых тропической морской анемоной Heteractis crispa (=Heteractis magnifica, ранее Radianthus macrodactylus). Одним из основных достижений лаборатории за прошедшие годы является открытие нового структурного типа 2 нейротоксинов, а именно шести токсинов, которые в первое десятилетие зарубежных исследований (70–80-е годы прошлого столетия) не были идентифицированы среди представителей так называемых длинных анемонотоксинов, и среди них – первого, ранее неизвестного, двухцепочечного нейротоксина. Кроме того, установлено наличие нескольких мультигенных семейств, экспрессирующих a-пороформирующие токсины (актинопорины), ингибиторы сериновых протеаз (пептиды Кунитц-типа) и APETx-подобные пептиды, образующих комбинаторные библиотеки, насчитывающие по нескольку десятков высокогомологичных представителей семейства. Методами in silico (гомологичное моделирование, аланиновый мутагенез, полноатомная молекулярно-динамическая (МД) симуляция) впервые предсказаны пространственные структуры исследуемых пептидов и комплексов с биологическими мишенями, проведен анализ их структурно-функциональных взаимоотношений. Это явилось основой для дальнейшего получения на базе комбинаторных библиотек рекомбинантных и мутантных аналогов с целью проведения электрофизиологических исследований механизмов их молекулярного взаимодействия с мишенями, а также определения фармакологического потенциала. В обзоре кратко представлены наиболее важные результаты последних лет, связанные с открытием у ряда исследуемых пептидов анальгетической, противовоспалительной и противоопухолевой активности.

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