Department of Chemistry, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.
ACS Infect Dis. 2021 Mar 12;7(3):681-692. doi: 10.1021/acsinfecdis.1c00015. Epub 2021 Mar 3.
The spatial and temporal control of bioactivity of small molecules by light (photopharmacology) constitutes a promising approach for study of biological processes and ultimately for the treatment of diseases. In this study, we investigated two different "caged" antibiotic classes that can undergo remote activation with UV-light at λ = 365 nm, via the conjugation of deactivating and photocleavable units through a short synthetic sequence. The two widely used antibiotics vancomycin and cephalosporin were thus enhanced in their performance by rendering them photoresponsive and thereby suppressing undesired off-site activity. The antimicrobial activity against ATCC 6633, ATCC 29213, ATCC 43300 (MRSA), ATCC 25922, and ATCC 27853 could be spatiotemporally controlled with light. Both molecular series displayed a good activity window. The vancomycin derivative displayed excellent values against Gram-positive strains after uncaging, and the next-generation caged cephalosporin derivative achieved good and broad activity against both Gram-positive and Gram-negative strains after photorelease.
通过光（光药理学）对小分子生物活性的时空控制，为研究生物过程并最终治疗疾病提供了一种很有前途的方法。在这项研究中，我们研究了两种不同的“笼状”抗生素类，它们可以通过通过短的合成序列将失活和光解单元连接起来，用 λ = 365nm 的 UV 光远程激活。两种广泛使用的抗生素万古霉素和头孢菌素通过使它们对光有反应性，从而抑制了不需要的非靶向活性，从而提高了它们的性能。可以用光时空控制来控制对 ATCC 6633、ATCC 29213、ATCC 43300（MRSA）、ATCC 25922 和 ATCC 27853 的抗菌活性。这两个分子系列都显示出了很好的活性窗口。在去笼后，万古霉素衍生物对革兰氏阳性菌株表现出极好的活性，而下一代的笼状头孢菌素衍生物在光释放后对革兰氏阳性和革兰氏阴性菌株都表现出良好而广泛的活性。
