Details

Autor(en) / Beteiligte

• Xin-Meng Fan Xian-Tao Yang Yu-Jia Guo Ren-Min Wu De-Lin Pan Zhu Guan Xiao-Mei Ling Li-He Zhang Zhen-Jun Yang

Titel

Insight into the deamination mechanism of 6-cyclopropylamino guanosine analogs for anti-HIV drug design

Ist Teil von

• 中国化学快报：英文版, 2016 (12), p.1759-1762

Erscheinungsjahr

2016

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Deamination is a crucial step in the transformation of 6-cyclopropylamino guanosine prodrug to its active form. A convenient method using capillary electrophoresis(CE) without sample labeling was developed to analyze the deamination of a series of D-/L-6-cyclopropylamino guanosine analogs by mouse liver homogenate, mouse liver microsome, and adenosine deaminase(ADA). A two-step process involving a 6-amino guanosine intermediate formed by oxidative N-dealkylation was demonstrated in the metabolism of 6-cyclopropylamino guanosine to 6-hydroxy guanosine. The results indicated that the transformation rates of different prodrugs to the active form varied greatly, which were closely correlated with the configuration of nucleosides and the structure of glycosyl groups. Most importantly,D-form analogs were metabolized much faster than their L-counterparts, thus clearly pointed out that compared to guanine, modification of glycosyl part might be a better choice for the development of L-guanosine analogs for the treatment of HIV.