Synthesis and flow cytometric evaluation of novel 1,2,3,4-tetrahydroisoquinoline conformationally constrained analogues of nitrobenzylmercaptopurine riboside (NBMPR) designed for probing its conformation when bound to the es nucleoside transporter.
Synthesis and flow cytometric evaluation of novel 1,2,3,4-tetrahydroisoquinoline conformationally constrained analogues of nitrobenzylmercaptopurine riboside (NBMPR) designed for probing its conformation when bound to the es nucleoside transporter.
复制标题
硝基苄基巯基嘌呤核苷 (NBMPR) 的新型 1,2,3,4-四氢异喹啉构象受限类似物的合成和流式细胞术评估，旨在探测其与 es 核苷转运蛋白结合时的构象。
DOI：
10.1021/jm020405p
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发表时间：
2003
影响因子：
7.3
通讯作者：
Buolamwini,JohnK
中科院分区：
文献类型：
--
作者：
Zhu,Zhengxiang;Furr,John;Buolamwini,JohnK
Novel regioisomers of conformationally constrained analogues of the potentesnucleoside transporter ligand, nitrobenzylmercaptopurine riboside (NBMPR), designed for probing its bound (bioactive) conformation, were synthesized and evaluated asestransporter ligands by flow cytometry. Purine 6-position 5, 6, 7, or 8-nitro-1,2,3,4-tetrahydroisoquinolylpurine ribosides, in which the nitrobenzyl moiety in NBMPR has been locked into the nitro-1,2,3,4-tetrahydroisoquinoline system, were synthesized by reaction of the appropriate nitro-1,2,3,4-tetrahydroisoquinoline with 6-chloropurine riboside. Flow cytometry was performed using 5-(SAENTA)-X8-fluorescein as the competitive ligand. A high degree of variation in theestransporter binding capacity of the target compounds was observed, with theKivalues ranging from 0.45 nM for the most tightly bound compound (4) to 300 nM for the least tightly bound compound (5). TheKiof NBMPR was 0.70 nM, a little higher than that of compound4. Compound4is the isomer that has the nitro group in the best orientation at theestransporter binding site compared to the other three compounds,2,3, and5.
