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Новости химической науки > Боеголовка двойного действия убьет и обезвредит бактерии


4.6.2014
средняя оценка статьи - 2.5 (6 оценок) Подписаться на RSS

Исследователи из Индии разработали соединение, которое убивает бактерии и разрушает их ДНК, препятствуя формирования генов, обеспечивающих резистентность к антибиотикам.

Возрастающая проблема с понижением эффективности существующих антибиотиков, а также отсутствие достаточного количества подходящих антибиотиков новых типов представляет уже давно и активно обсуждается медицинским сообществом. Как отмечает Главный государственный санитарный врач Великобритании, за последние 20 лет наметилась печальная тенденция к увеличению смертельных случаев, вызванных постоперационными инфекциями или больничными инфекциями другого типа, с которыми ранее справлялись традиционные антибиотики.

Своеобразной «ахиллесовой пятой» бактерий является мембрана клеток микроорганизмов – роль этого органоида весьма важна в жизни и выживании бактерии. В качестве лекарственных препаратов, воздействующих на мембрану бактерий, используются противомикробные пептиды [antimicrobial peptides (AMP)], однако это оружие против бактерий отличается высокой себестоимостью производства, оно легко разрушается, и его весьма сложно доставлять по адресу. Разработанные исследователями из группы Аягари Рамеша (Aiyagari Ramesh) синтетические амфифильные молекулы, имитирующие противомикробные пептиды, лишены недостатков своих природных аналогов.



Рисунок из Chem. Commun., 2014, DOI: 10.1039/c4cc02354d

Разработанный синтетический аналог противомикробных пептидов содержат катионную пиридиниевую группу, обеспечивающую электростатическое взаимодействие, как с имеющей анионную природу поверхность бактериальной клетки, так и бактериальной ДНК, а также гидрофобный фрагмент, содержащий 12 атомов углерода – этот «хвост» способствует проникновению вещества через мембрану клетки. Также новое соединение содержит плоский флуорогенный пиреновый фрагмент, который позволял системе не только взаимодействовать с ДНК, но и отслеживать это взаимодействие с помощью спектральных методов.

Таким образом, полученное соединение атакует бактерию двумя путями – оно убивает бактерию, разрушая ее клеточную мембрану, а также нарушает механизм выработки резистетности, блокируя участки ДНК, которые отвечают за механизм возникновения зашиты бактерий от антибиотиков.

Джулиан Хёрдл (Julian Hurdle) из Университета Техаса (Арлингтон), изучающий способы борьбы с резистентными патогенами, проявляет значительный интерес к предложенному подходу. Он подчеркивает, что мембраны представляют собой идеальную мишень для противомикробных агентов, способных бороться с патогенами, устойчивыми к действию антибиотиков.

Источник: Chem. Commun., 2014, DOI: 10.1039/c4cc02354d

метки статьи: #биохимия, #медицинская химия, #молекулярная биология

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