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Synthesis of three no-carrier-added O6-4-[125I] iodobenzylguanosine derivatives, new reagents for the assay of O6-alkylguanine-DNA alkyltransferase activity

✍ Scribed by Emmanuelle Mounetou; Catherine Cussac; Frédérique Mathieu; Jean-Claude Maurizis; Pierre Labarre; Marie-France Moreau; Annie Veyre; Jean-Claude Madelmont


Publisher
John Wiley and Sons
Year
1995
Tongue
French
Weight
461 KB
Volume
36
Category
Article
ISSN
0022-2135

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✦ Synopsis


Abstract

O^6^‐alkylguanine‐DNA alkyltransferase (AGT) is mainly responsible for tumour resistances observed in chemotherapeutic treatments by chloroethylnitrosoureas (CENUs). Measurement of AGT activity is thereby essential to predict the response of the patients to therapy with CENUs. In order to develop a sensitive and easy new assay for AGT, previously undescribed O^6^‐4‐[^125^I]iodobenzyl‐2′‐deoxyguanosine, O^6^‐4‐ [^125^I]iodobenzyl‐N‐acetylguanosine and O^6^‐4‐[^125^I] iodobenzylguanosine labelled with high specific activity were prepared. The most convenient synthetic route appeared to be a rapid and high yield iododestannylation of a tri‐n‐butylstannyl derivative with no‐carrieradded sodium [^125^I] iodide. Final HPLC separation from the excess of precursor and unreacted [^125^I] iodides afforded the radioiodinated guanosine derivatives in yields ranging from 70 to 77 %, chemical and radiochemical purities averaging 99%.