Lau Vivian, Heyne Belinda
Chemistry Department, University of Calgary, Calgary, AB, Canada.
Photochem Photobiol. 2009 Sep-Oct;85(5):1110-5. doi: 10.1111/j.1751-1097.2009.00559.x. Epub 2009 Apr 6.
Singlet oxygen is known to be a potent mutagenic agent and several biologically relevant molecules have been proposed to act as scavengers for this noxious species. However, numerous studies have been conducted in homogenous solution and the reactivity of singlet oxygen scavengers known to bind DNA has never been investigated in double-stranded DNA. In the following paper, we present the results obtained regarding the interaction between 4',6-diamidino-2-phenylindole (DAPI) and singlet oxygen. We show the molecule to be a potent scavenger of singlet oxygen in aqueous solution with an absolute rate constant (chemical and physical quenching of singlet oxygen) of (1.7+/-0.3)x10(7) m(-1) s(-1). In addition, we demonstrate that the binding mode of a singlet oxygen scavenger to DNA can strongly influence its reactivity toward singlet oxygen. In the case of DAPI, while the molecule exhibits a chemical reaction with singlet oxygen when the molecule is free in aqueous solution or intercalated in GC sequences of DNA, DAPI becomes chemically unreactive toward singlet oxygen when bound in the minor groove of DNA AT sequences.
单线态氧是一种已知的强效诱变剂，已有几种与生物学相关的分子被提出可作为这种有害物质的清除剂。然而，许多研究是在均相溶液中进行的，已知能与DNA结合的单线态氧清除剂在双链DNA中的反应活性从未被研究过。在接下来的论文中，我们展示了关于4',6-二脒基-2-苯基吲哚（DAPI）与单线态氧相互作用的研究结果。我们发现该分子在水溶液中是一种强效的单线态氧清除剂，其绝对速率常数（单线态氧的化学和物理猝灭）为(1.7±0.3)×10⁷ m⁻¹ s⁻¹。此外，我们证明单线态氧清除剂与DNA的结合模式会强烈影响其对单线态氧的反应活性。就DAPI而言，当该分子在水溶液中游离或嵌入DNA的GC序列时，它会与单线态氧发生化学反应，但当它结合在DNA AT序列的小沟中时，对单线态氧就变得没有化学反应活性了。
