ранпирназа

Рибонуклеазы с антипролиферативной активностью: молекулярно-биологические и биохимические свойства

ЭКСПЕРИМЕНТАЛЬНЫЕ ИССЛЕДОВАНИЯ , , , , ,

В.С. Покровский1, Е.М. Трещалина1, Н.В. Андронова1, С.М. Деев2

1 ФГБУ «Российский онкологический научный центр им. Н.Н. Блохина» Минздрава России, Каширское ш., д. 24, Москва, Российская Федерация, 115478

2 ФГБУН «Институт биоорганической химии им. акад. М.М. Шемякина и Ю.А. Овчинникова» РАН, ул. Миклухо-Маклая, д. 16/10, Москва, Российская Федерация, 117997

Для переписки: Вадим Сергеевич Покровский, канд. мед. наук, Каширское ш., д. 24, Москва, Российская Федерация, 115478; тел.: +7(499)324-14-09; e-mail: vadimpokrovsky@yandex.ru

Для цитирования: Покровский В.С., Трещалина Е.М., Андронова Н.В., Деев С.М. Рибонуклеазы с антипролиферативной активностью: молекулярно-биологические и биохимические свойства. Клиническая онкогематология. 2016;9(2):130–7.

DOI: 10.21320/2500-2139-2016-9-2-130-137

РЕФЕРАТ

Статья посвящена рибонуклеазам (РНКазы), цитотоксический эффект которых определяется ферментативной активностью, т. е. способностью катализировать расщепление фосфодиэфирных связей РНК. Представлены известные и собственные данные о РНКазах с противоопухолевыми свойствами различного происхождения, проведен поиск параллелей между механизмами цитотоксичности, биохимическими и молекулярно-биологическими свойствами. Анализ данных литературы дает возможность считать, что все перечисленные свойства вносят свой вклад в антипролиферативное действие РНКаз. Основной проблемой для этого ряда ферментов остается достижение селективной биодоступности. Это решается путем создания конъюгатов, как это показано для ранпирназы и барназы. По основным фармакологическим характеристикам активные противоопухолевые РНКазы перспективны не только в онкогематологии, но и при терапии солидных опухолях.

Ключевые слова: рибонуклеаза, ранпирназа, амфиназа, биназа, барназа, фармакологические характеристики.

Получено: 4 января 2016 г.

Принято в печать: 7 января 2016 г.

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Ферментные препараты в онкогематологии: актуальные направления экспериментальных исследований и перспективы клинического применения

ОБЗОРЫ , , , , , ,

В.С. Покровский, Е.М. Трещалина

ФГБУ «Российский онкологический научный центр им. Н.Н. Блохина» РАМН, Москва, Российская Федерация

РЕФЕРАТ

Последние годы в области разработки новых противоопухолевых препаратов на основе ферментов продемонстрированы существенные достижения. Помимо L-аспарагиназы, которая применяется в онкогематологии уже более 30 лет, два фермента — L-аргининдезиминаза и ранпирназа — прошли несколько этапов клинических исследований. Для целого ряда ферментов показана противоопухолевая активность на доклиническом этапе в экспериментах in vivo: L-метионин-гамма-лиаза, L-лизин-альфа-оксидаза, биназа. В настоящем обзоре представлены ферменты, продемонстрировавшие на различных этапах исследований противоопухолевую активность, и перспективы их использования в онкогематологии.

Ключевые слова: противоопухолевые ферменты, L-аспарагиназа, L-метионин-гамма-лиаза, L-лизин-альфа-оксидаза, L-аргининдезиминаза, L-фенилаланин-аммиак-лиаза, ранпирназа.

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