|
ИСТИНА |
Войти в систему Регистрация |
Интеллектуальная Система Тематического Исследования НАукометрических данных |
||
High-Affinity alpha-Conotoxin PnIA Analogs Designed on the Basis of the Protein Surface Topography Methodстатья
Статья опубликована в высокорейтинговом журнале
Статья опубликована в журнале из списка Web of Science и/или Scopus- Авторы: Kasheverov Igor E., Chugunov Anton O., Kudryavtsev Denis S., Ivanov Igor A., Zhmak Maxim N., Shelukhina Irina V., Spirova Ekaterina N., Tabakmakher Valentin M., Zelepuga Elena A., Efremov Roman G., Tsetlin Victor I.
- Журнал: Scientific reports
- Том: 6
- Год издания: 2016
- Издательство: Nature Publishing Group
- Местоположение издательства: United Kingdom
- DOI: 10.1038/srep36848
- Аннотация: Despite some success for small molecules, elucidating structure-function relationships for biologically active peptides-the ligands for various targets in the organism-remains a great challenge and calls for the development of novel approaches. Some of us recently proposed the Protein Surface Topography (PST) approach, which benefits from a simplified representation of biomolecules’ surface as projection maps, which enables the exposure of the structure-function dependencies. Here, we use PST to uncover the “activity pattern” in alpha-conotoxins-neuroactive peptides that effectively target nicotinic acetylcholine receptors (nAChRs). PST was applied in order to design several variants of the alpha-conotoxin PnIA, which were synthesized and thoroughly studied. Among the best was PnIA[R9, L10], which exhibits nanomolar affinity for the alpha 7 nAChR, selectivity and a slow wash-out from this target. Importantly, these mutations could hardly be delineated by “standard” structure-based drug design. The proposed combination of PST with a set of experiments proved very efficient for the rational construction of new bioactive molecules.
- Добавил в систему: Кудрявцев Денис Сергеевич