tetano
Editor, Senior Moderator
Bioorg Med Chem. 2019 May 17. pii: S0968-0896(19)30535-8. doi: 10.1016/j.bmc.2019.05.024. [Epub ahead of print]
[h=1]Investigation of flexibility of neuraminidase 150-loop using tamiflu derivatives in influenza A viruses H1N1 and H5N1.[/h] Zima V[SUP]1[/SUP], Albi?ana CB[SUP]1[/SUP], Roj?kov? K[SUP]2[/SUP], Pokorn? J[SUP]3[/SUP], Pachl P[SUP]3[/SUP], Řez?čov? P[SUP]4[/SUP], Hudlicky J[SUP]1[/SUP], Navr?til V[SUP]3[/SUP], Majer P[SUP]3[/SUP], Konvalinka J[SUP]5[/SUP], Ko???ek M[SUP]3[/SUP], Machara A[SUP]6[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] This study focuses on design, synthesis and in vitro evaluation of inhibitory potency of two series of sialylmimetic that target an exosite ("150-cavity") adjacent to the active site of influenza neuraminidases from A/California/07/2009 (H1N1) pandemic strain and A/chicken/Nakorn-Patom/Thailand/CU-K2-2004 (H5N1). The structure-activity analysis as well as 3-D structure of the complex of parental compound with the pandemic neuraminidase p09N1 revealed high flexibility of the 150-cavity towards various modification of the neuraminidase inhibitors. Furthermore, our comparison of two methods for inhibition constant determination performed at slightly different pH values suggest that the experimental conditions of the measurement could dramatically influence the outcome of the analysis in the compound-dependent manner. Therefore, previously reported K[SUB]i[/SUB] values determined at non-physiological pH should be carefully scrutinized.
Copyright ? 2019 Elsevier Ltd. All rights reserved.
[h=4]KEYWORDS:[/h] Click chemistry; Crystal structure; Influenza neuraminidase; Oseltamivir
PMID: 31128993 DOI: 10.1016/j.bmc.2019.05.024
[h=1]Investigation of flexibility of neuraminidase 150-loop using tamiflu derivatives in influenza A viruses H1N1 and H5N1.[/h] Zima V[SUP]1[/SUP], Albi?ana CB[SUP]1[/SUP], Roj?kov? K[SUP]2[/SUP], Pokorn? J[SUP]3[/SUP], Pachl P[SUP]3[/SUP], Řez?čov? P[SUP]4[/SUP], Hudlicky J[SUP]1[/SUP], Navr?til V[SUP]3[/SUP], Majer P[SUP]3[/SUP], Konvalinka J[SUP]5[/SUP], Ko???ek M[SUP]3[/SUP], Machara A[SUP]6[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] This study focuses on design, synthesis and in vitro evaluation of inhibitory potency of two series of sialylmimetic that target an exosite ("150-cavity") adjacent to the active site of influenza neuraminidases from A/California/07/2009 (H1N1) pandemic strain and A/chicken/Nakorn-Patom/Thailand/CU-K2-2004 (H5N1). The structure-activity analysis as well as 3-D structure of the complex of parental compound with the pandemic neuraminidase p09N1 revealed high flexibility of the 150-cavity towards various modification of the neuraminidase inhibitors. Furthermore, our comparison of two methods for inhibition constant determination performed at slightly different pH values suggest that the experimental conditions of the measurement could dramatically influence the outcome of the analysis in the compound-dependent manner. Therefore, previously reported K[SUB]i[/SUB] values determined at non-physiological pH should be carefully scrutinized.
Copyright ? 2019 Elsevier Ltd. All rights reserved.
[h=4]KEYWORDS:[/h] Click chemistry; Crystal structure; Influenza neuraminidase; Oseltamivir
PMID: 31128993 DOI: 10.1016/j.bmc.2019.05.024