Radiolabeled Guanine Derivatives for the in Vivo Mapping of O6-Alkylguanine-DNA Alkyltransferase: 6-(4-[18F]Fluoro-benzyloxy)-9H-purin-2-ylamine and 6-(3-[131I]Iodo-benzyloxy)-9H-purin-2-ylamine
- 25 October 2000
- journal article
- research article
- Published by American Chemical Society (ACS) in Bioconjugate Chemistry
- Vol. 11 (6) , 868-875
- https://doi.org/10.1021/bc0000435
Abstract
Two radiolabeled analogues of 6-benzyloxy-9H-purin-2-ylamine (O6-benzylguanine; BG) potentially useful in the in vivo mapping of O6-alkylguanine-DNA alkyltransferase (AGT) were synthesized. Fluorine-18 labeling of the known 6-(4-fluoro-benzyloxy)-9H-purin-2-ylamine (FBG; 6) was accomplished by the condensation of 4-[18F]fluorobenzyl alcohol with 2-aminopurin-6-yltrimethylammonium chloride (4) or 2-amino-6-chloropurine in average decay-corrected radiochemical yields of 40 and 25%, respectively. Unlabeled 6-(3-iodo-benzyloxy)-9H-purin-2-ylamine (IBG; 7) was prepared from 4 and 3-iodobenzyl alcohol. Radioiodination of 9, prepared from 7 in two steps, and subsequent deprotection gave [131I]7 in about 70% overall radiochemical yield. The IC50 values for the inactivation of AGT from CHO cells transfected with pCMV-AGT were 15 nM for IBG and 50 nM for FBG. The binding of [18F]6 and [131I]7 to purified AGT was specific and saturable with both exhibiting similar IC50 values (5−6 μM).Keywords
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