vestichИзвестия Национальной академии наук Беларуси. Серия химических наукProceedings of the National Academy of Sciences of Belarus, Chemical Series1561-83312524-2342The Republican Unitary Enterprise Publishing House "Belaruskaya Navuka"vestich-260Research ArticleОБЗОРЫФАГОВЫЙ ДИСПЛЕЙ В КОНСТРУИРОВАНИИ АНТИТЕЛ С ЗАДАННЫМИ СВОЙСТВАМИPHAGE DISPLAY IN ENGINEERING OF ANTIBODIES WITH DESIRED PROPERTIESДормешкинД. О.DormeshkinD. O.

науч. сотрудник

Researcher

dormeshkin@gmail.comБричкоЕ. А.BrichkoE. A.

студент

Student

kate.bri13@gmail.comГилепА. А.GilepA. A.

канд. хим. наук, зав. отделом молекулярных биотехнологий

Ph.D. (Chemistry), Head of the Department of molecular biotechnologies

agilep@iboch.basnet.byУсановС. А.UsanovS. A.

член-кор., д-р хим. наук

Corr. Member of the National Academy of Sciences, D. Sc. (Chemistry), Professor

usanov@iboch.bas-net.byИнститут биоорганической химии НАН БеларусиInstitute of Bioorganic Chemistry of the National Academy of Sciences of BelarusБелорусский государственный университетBelarusian State University2017080820170293110Copyright © Дормешкин Д.О., Бричко Е.А., Гилеп А.А., Усанов С.А., 20172017Дормешкин Д.О., Бричко Е.А., Гилеп А.А., Усанов С.А.Dormeshkin D.O., Brichko E.A., Gilep A.A., Usanov S.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vestichem.belnauka.by/jour/article/view/260

Уникальная особенность моноклональных антител высокоспецифично взаимодействовать с молекулярными мишенями позволила им занять ведущее положение в терапии онкологических и аутоиммунных заболеваний, стать незаменимым инструментом протеомных исследований и компонентом диагностических систем. Представлен обзор новейших литературных данных по использованию метода фагового дисплея для получения рекомбинантных антител, которые другими методами получить невозможно, а также собственные оригинальные результаты в этой области. На основании бионформационного анализа структур депонированных комплексов антител с антигенами нами создана комбинаторная библиотеки Fab фрагментов антител человека, обладающая разнообразием более 1010 независимых клонов и способная служить источником рекомбинантных антител. С использованием негативной селекции нами получены и характеризованы высокоспецифичные однодоменные антитела к альдостерон-синтазе (цитохром Р45011В2, CYP11B2), не обладающие в ИФА кросс-реактивностью с ее гомологом CYP11B1 (93% идентичности последовательностей), а также антитела к таким высокомолекулярным мишеням, как эритропоэтин, соматотропный гормон и тиреопероксидаза человека. 

Antibodies are an essential tool being a part of immunodiagnostics, therapeutics and life science research instruments. In this paper we analyze the recent developments in recombinant antibodies generation by means of phage display technology. We also provide our own results dedicated to antibodies development process. Analysis of antibody-antigen complexes with resolved structures allow to create synthetic phage display library of Fab antibody fragments with the diversity of 1010 independent clones. Utilizing a negative selection approach, we succeeded in generation and characterization of specific single-domain antibodies that has substantially different binding kinetics to CYP11B2 and CYP11B1 isoenzymes – proteins with 93% sequence identity. We also generated specific binders to a few high-molecular weight human antigens – erytropoetin, growth hormone and thyroperoxidase.

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The authors declare that there are no conflicts of interest present.