chemicallytechFine Chemical TechnologiesТонкие химические технологии2410-65932686-7575MIREA – Russian Technological University (RTU MIREA).chemicallytech-478Research ArticleCHEMISTRY AND TECHNOLOGY OF MEDICINAL COMPOUNDS AND BIOLOGICALLY ACTIVE SUBSTANCESХИМИЯ И ТЕХНОЛОГИЯ ЛЕКАРСТВЕННЫХ ПРЕПАРАТОВ И БИОЛОГИЧЕСКИ АКТИВНЫХ СОЕДИНЕНИЙPegylation, as method of production prolonged forms of biopharmaceutical drugs (pegylated granulocyte colony-stimulating factor as case of study)Пэгилирование как метод создания пролонгированных форм биофармацевтических препаратов (на примере пэгилированного гранулоцитарного колониестимулирующего фактора)ПучковИ. А.PuchkovI. А.

кафедра Биотехнологии и бионанотехнологии, аспирант

poutchkov@mail.ruБаирамашвилиД. И.BairamashviliD. I.

начальник производства

noemail@neicon.ruШвецВ. И.ShvetsV. I.

кафедра Биотехнологии и бионанотехнологии, заведующий кафедрой, академик РАН

noemail@neicon.ruМИТХТ им. М.В. Ломоносова, 119571, Москва, пр-т Вернадского, д. 86; Российская фармацевтическая компания ЗАО «Мастерклон», Москва, 119019РоссияM.V. Lomonosov Moscow State University of Fine Chemical Technologies, 86, Vernadskogo pr., Moscow 119571; Russian Pharmaceutical Company «Masterclone», Moscow, 119019Russian FederationОпытное биотехнологическое производство генно-инженерных препаратов ИБХ РАН, Москва, 117997РоссияTest Biotechnological Production of the Genetically Engineered Preparations of M.M. Shemyakin and Yu.A. Ovchinnikov Institute of Bioorganic Chemistry RAS, Moscow, 117997Russian FederationМИТХТ им. М.В. Ломоносова, 119571, Москва, пр-т Вернадского, д. 86Russian Federation20142804201492331Copyright © Puchkov I.А., Bairamashvili D.I., Shvets V.I., 20142014Пучков И.А., Баирамашвили Д.И., Швец В.И.Puchkov I.А., Bairamashvili D.I., Shvets V.I.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.finechem-mirea.ru/jour/article/view/478

By now the pegylation of biologically active molecules including proteins with an inert hydrophilic polymer polyethylene glycol (PEG) is an important area in the new generation of prolonged-action pharmaceutical preparations. The conjugated molecules usually have an improved pharmacokinetic profile, including reduced renal clearance, additional protection from the proteolytic enzymes and reduced immunogenicity, thus preserving the in vivo activity of the native preparation in the human body for a longer time. This review is focused on the example of the pegylation of recombinant human granulocyte colony-stimulating factor (G-CSF) and gives the opportunity to have a look at different ways of pegylation and the mechanism of this reaction. Besides, the review describes the different types of reactive PEG for the specific conjugation to biological molecules and benefits and disadvantages of these reagents.

В настоящее время пэгилирование биологически активных молекул, в том числе белков, с помощью инертного гидрофильного полимера полиэтиленгликоля (ПЭГ) представляет собой важное направление в создании нового поколения фармацевтических препаратов пролонгирован-ного действия. Конъюгированные молекулы, как правило, имеют улучшенный фармакокинетический профиль, в том числе пониженный почечный клиренс, дополнительную защиту от действия протео-литических ферментов и низкую иммуногенность, что позволяет сохранить активность in vivo нативного препарата в человеческом организме в течение более продолжительного времени. Данный обзор дает возможность ознакомиться с современными методиками пэгилирования биофармацев-тических молекул, препаратами на основе конъюгатов с ПЭГ и рассматривает, как пример, пэгилирование рекомбинантного человеческого гранулоцитарного колониестимулирующего фактора (рчГ-КСФ). Также в обзоре представлены различные виды модифицированных ПЭГ-реагентов для направленного присоединения к биологическим молекулам и обсуждаются их преимущества и недостатки.

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