Two-dimensional NMR studies on the anthramycin-d(ATGCAT)2 adduct.
Two-dimensional NMR studies on the anthramycin-d(ATGCAT)2 adduct.
复制标题
蒽霉素-d(ATGCAT)2 加合物的二维 NMR 研究。
DOI：
10.1021/bi00452a017
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发表时间：
1989
期刊：
影响因子：
2.9
通讯作者：
Stone,MP
中科院分区：
文献类型：
--
作者：
Krugh,TR;Graves,DE;Stone,MP
罗切斯特大学化学系，罗切斯特，纽约14627，密西西比大学化学系，密西西比大学38677，和范德比尔特大学化学系，纳什维尔，田纳西37235接收日期：1989年6月12日摘要：对氨霉素与d-（ATGCAT）2的加合物进行了二维NMR实验，以获得核苷酸碱基和糖质子以及氨霉素质子的归属。蒽霉素与鸟嘌呤2-氨基共价连接，形成d（ATamGCAT）* d-（ATGCAT）修饰的双链体。小沟区的氨霉素质子对几个核苷酸质子有NOE效应。安曲霉素-核苷酸NOE的网络和安曲霉素H11和H11 a质子之间的10-Hz偶合常数的测量表明，安曲霉素作为S立体异构体共价连接在安曲霉素C11位置，安曲霉素的侧链朝向修饰链的5 '端。NOE数据表明，蒽霉素修饰的双链体是在一个反构象的所有碱基的右手构象。氨曲霉素（图1）是一种有效的抗肿瘤抗生素，它与含鸟苷的双链体DNA共价反应，形成跨越四个碱基对区域的加合物[关于吡咯并[1，4]苯并二氮杂抗生素的综述，参见Hurley和Needham-VanDevanter（1986）]。Hurley和Petrusek（1979年）以及Petrusek et al.（1981）得出结论，氨霉素与鸟嘌呤的环外氨基形成小沟加合物。~（13）C和~（13）H NMR实验证实了这一结论，并证明了氨霉素Cl ~ 1的存在
Department of Chemistry, University of Rochester, Rochester, New York 14627, Department of Chemistry, University of Mississippi, University, Mississippi 38677, and Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37235 Received June 12, 1989 abstract: Two-dimensional NMR experiments were performed on the adduct of anthramycin with d-(ATGCAT) 2 to obtain the assignments of the nucleotide base and sugar protons as well as the anthramycin protons. Anthramycin is covalently attached to a guanine 2-amino group, forming the d (ATamGCAT)* d-(ATGCAT) modified duplex. The anthramycin protons inthe minor groove exhibit NOEs to several nucleotide protons. The network of anthramycin-nucleotide NOEs and the measurement of the 10-Hz coupling constant between the anthramycin HI 1 and HI la protons shows that anthramycin is covalently attached as the S stereoisomer at the anthramycin Cl 1 position with the side chain of anthramycin oriented toward the 5'end of the modified strand. The NOE data show that the anthramycin-modified duplex is in a right-handed conformation with all bases in an anti conformation. Analysis of the coupling constants for the resolved HI'resonances shows that the S-type conformation of the sugars is highly preferred.Amthramycin (Figure 1) is a potent antitumor antibiotic which reacts covalently with guanosine-containing duplex DNA to form an adduct that spans a four base pair region [for a review of pyrrolo [1, 4] benzodiazepine antibiotics, see Hurley and Needham-VanDevanter (1986)]. Hurley and Petrusek (1979) and Petrusek et al.(1981) concluded that anthramycin forms a minor groove adduct with the exocyclic amino group of guanine. Carbon-13 and proton NMR ex-periments confirmed this conclusion and demonstrated the anthramycin Cl 1