Chemical Probes for Drug??Resistance Assessment by Binding Competition (RABC): Oseltamivir Susceptibility Evaluation

…, HS Wu, NS Wang, CK Cheng, CL Chen…

Index: Cheng, Ting-Jen R.; Wang, Shi-Yun; Wen, Wen-Hsien; Su, Ching-Yao; Lin, Mengi; Wen-I Huang; Liu, Ming-Tsan; Wu, Ho-Sheng; Wang, Nung-Sen; Cheng, Chung-Kai; Chen, Chun-Lin; Ren, Chien-Tai; Wu, Chung-Yi; Fang, Jim-Min; Cheng, Yih-Shyun E.; Wong, Chi-Huey Angewandte Chemie - International Edition, 2013 , vol. 52, # 1 p. 366 - 370

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Citation Number: 7

Abstract

For the treatment of influenza infections, neuraminidase (NA) inhibitors oseltamivir (Tamiflu) and zanamivir (Relenza) are the most useful therapies.[1–3] Oseltamivir is an oral prodrug that is converted by an endogenous esterase to oseltamivir carboxylate (OS, 1, Figure 1). Upon the binding of OS to NA, an induced fit of NA to reorient the Glu276 residue toward Arg224 creates a larger hydrophobic pocket for the side chain of OS.[4, 5] NAs can evolve ...