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通过与卟啉相连的反义寡脱氧核苷酸对HIV衍生的寡核糖核苷酸进行靶向光化学修饰。

Targeted photochemical modification of HIV-derived oligoribonucleotides by antisense oligodeoxynucleotides linked to porphyrins.

作者信息

Mastruzzo L, Woisard A, Ma D D, Rizzarelli E, Favre A, Le Doan T

机构信息

Laboratoire de Chimie, CNRS URA 401, Paris, France.

出版信息

Photochem Photobiol. 1994 Oct;60(4):316-22. doi: 10.1111/j.1751-1097.1994.tb05110.x.

DOI:10.1111/j.1751-1097.1994.tb05110.x
PMID:7991660
Abstract

Antisense oligodeoxynucleotides directed against a 24-mer RNA derived from the long terminal repeat (LTR) region of HIV were linked to proto- and methylpyrroporphyrin and their zinc derivatives. The oligonucleotide-porphyrin conjugates were tested for their ability to induce photodamage on the target RNA. Upon hybridization followed by irradiation at 405 nm, the photochemical reaction led to photocross-linking of the antisense derivative to the RNA substrate. The protoporphyrin exhibited a much higher cross-linking yield than the methylpyrroporphyrin while the Zn-porphyrin derivatives were found to be less efficient than their corresponding nonmetallated congeners. The specificity of the photocross-linking reaction between the porphyrin-oligomer and its target RNA was demonstrated by the following evidence: (1) hybrid formation was required for photocross-linking to occur, (2) the sites of cross-linking on the target RNA were identified at G residues located in close proximity to the porphyrin photoactive center in the hybrid and (3) addition of bulk calf liver RNA did not affect the photocross-linking efficiency.

摘要

针对源自HIV长末端重复序列(LTR)区域的一段24聚体RNA的反义寡脱氧核苷酸,与原卟啉和甲基卟啉及其锌衍生物相连。测试了寡核苷酸 - 卟啉缀合物对靶RNA诱导光损伤的能力。杂交后在405nm处进行照射,光化学反应导致反义衍生物与RNA底物发生光交联。原卟啉表现出比甲基卟啉高得多的交联产率,而锌卟啉衍生物被发现比其相应的未金属化同类物效率更低。卟啉 - 低聚物与其靶RNA之间光交联反应的特异性由以下证据证明:(1)光交联发生需要杂交形成;(2)在杂交体中靠近卟啉光活性中心的G残基处确定了靶RNA上的交联位点;(3)添加大量小牛肝RNA不影响光交联效率。

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