Молекулярная пептидная трансплантация как инструмент создания биопептидов нового поколения: мини-обзор

Молекулярная пептидная трансплантация (МПТ) — это выделение/синтез биоактивного фрагмента пептида/белка и последующий перенос его в целевой белок/пептид для создания нового белкового продукта, обладающего заданными уникальными биологическими свойствами. Это один из способов, наряду с методами циркуляризации пептидной основы и молекулярным сшиванием, направленных на усиление структурной организации коротких пептидов. Исследования МПТ в настоящее время в основном сосредоточены на демонстрации ее полезности и применимости, а не на разработке получения биопептидов нового поколения. Цель мини-обзора — показать применимость метода МПТ для разработки стабильных и биодоступных пептидов нового поколения с улучшенными биологическими свойствами. Для создания таких пептидов важно правильно подобрать каркас для последующей прививки к нему биологически активной пептидной последовательности. К пептидам с необходимым каркасом относятся циклотиды, которые можно получить трехфазным синтезом. Циклотиды обладают общим механизмом действия. Их биологическая активность определяется способностью связывать белки с образованием пор и разрушением биологических мембран-мишеней, а также свойствами, необходимыми для создания на их каркасе новых пептидов. Для обеспечения функциональности новых биопептидов, полученных методом МПТ, можно использовать различные пептидные вставки. Примером эффективного практического применения МПТ являются различные пептидные лекарства. Следовательно, МПТ позволяет эффективно конструировать биопептиды нового поколения, отличающиеся высокой термодинамической и метаболической стабильностью эпитопа и новыми или усиленными биологическими функциями. Однако эффективность полученных пептидов с использованием МПТ необходимо доказать в исследованиях in vitro и in vivo.

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