Investigation of flexibility of neuraminidase 150-loop using tamiflu derivatives in influenza A viruses H1N1 and H5N1
Autor: | Petr Pachl, Jana Pokorná, Ales Machara, Milan Kožíšek, Pavlína Řezáčová, Pavel Majer, Kateřina Rojíková, Václav Navrátil, Carlos Berenguer Albiñana, Jason Hudlicky, Jan Konvalinka, Václav Zima |
---|---|
Rok vydání: | 2019 |
Předmět: |
Oseltamivir
Viral protein Stereochemistry Clinical Biochemistry Pharmaceutical Science Neuraminidase medicine.disease_cause 01 natural sciences Biochemistry chemistry.chemical_compound Influenza A Virus H1N1 Subtype Drug Discovery medicine Humans Molecular Biology biology Strain (chemistry) Influenza A Virus H5N1 Subtype 010405 organic chemistry Organic Chemistry Active site Influenza a In vitro Influenza A virus subtype H5N1 0104 chemical sciences 010404 medicinal & biomolecular chemistry chemistry biology.protein Molecular Medicine |
Zdroj: | Bioorganicmedicinal chemistry. 27(13) |
ISSN: | 1464-3391 |
Popis: | 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 Ki values determined at non-physiological pH should be carefully scrutinized. |
Databáze: | OpenAIRE |
Externí odkaz: |