Long-range replica exchange molecular dynamics guided drug repurposing against tyrosine kinase PtkA of Mycobacterium tuberculosis was written by Nagpal, Priya;Jamal, Salma;Singh, Hina;Ali, Waseem;Tanweer, Sana;Sharma, Rahul;Grover, Abhinav;Grover, Sonam. And the article was included in Scientific Reports in 2020.Reference of 36703-88-5 This article mentions the following:
Abstract: Tuberculosis (TB) is a leading cause of death worldwide and its impact has intensified due to the emergence of multi drug-resistant (MDR) and extensively drug-resistant (XDR) TB strains. Protein phosphorylation plays a vital role in the virulence of Mycobacterium tuberculosis (M.tb) mediated by protein kinases. Protein tyrosine phosphatase A (MptpA) undergoes phosphorylation by a unique tyrosine-specific kinase, protein tyrosine kinase A (PtkA), identified in the M.tb genome. In the present study, we performed an extensive investigation of the conformational behavior of the intrinsically disordered domain (IDD) of PtkA using replica exchange mol. dynamics simulations. Long-term mol. dynamics (MD) simulations were performed to elucidate the role of IDD on the catalytic activity of kinase core domain (KCD) of PtkA. This was followed by identification of the probable inhibitors of PtkA using drug repurposing to block the PtpA-PtkA interaction. The inhibitory role of IDD on KCD has already been established; however, various analyses conducted in the present study showed that IDDPtkA had a greater inhibitory effect on the catalytic activity of KCDPtkA in the presence of the drugs esculin and inosine pranobex. The binding of drugs to PtkA resulted in formation of stable complexes, indicating that these two drugs are potentially useful as inhibitors of M.tb. In the experiment, the researchers used many compounds, for example, 4-Acetamidobenzoic acid,9-((2R,3R,4S,5R)-3,4-Dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-3H-purin-6(9H)-one,1-(Dimethylamino)propan-2-ol (3:1:3) (cas: 36703-88-5Reference of 36703-88-5).
4-Acetamidobenzoic acid,9-((2R,3R,4S,5R)-3,4-Dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-3H-purin-6(9H)-one,1-(Dimethylamino)propan-2-ol (3:1:3) (cas: 36703-88-5) belongs to tetrahydrofuran derivatives. THF (Tetrahydrofuran) is a stable compound with relatively low boiling point and excellent solvency. Oxidations have also proved to be valuable and efficient approaches to chiral tetrahydrofuran derivatives.Reference of 36703-88-5
Referemce:
Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem