Molecular modeling, dynamics and docking studies of Purine Nucleoside Phosphorylase from Streptococcus pyogenes

2009 ◽  
Vol 142 (1-3) ◽  
pp. 7-16 ◽  
Author(s):  
Luis Fernando Saraiva Macedo Timmers ◽  
Rafael Andrade Caceres ◽  
Raquel Dias ◽  
Luiz Augusto Basso ◽  
Diogenes Santiago Santos ◽  
...  
Keyword(s):  
Molecular Modeling ◽  
Streptococcus Pyogenes ◽  
Purine Nucleoside Phosphorylase ◽  
Docking Studies ◽  
Purine Nucleoside ◽  
Nucleoside Phosphorylase

scholarly journals Computer-aided rational design of acyclovir analogs to inhibit purine nucleoside phosphorylase

2019 ◽  
Author(s):  
Nusrat Jahan Selsi ◽  
Lira Barua ◽  
Debpriya Bhattacharjee ◽  
Gulamur Rahman ◽  
Syeda Sakiatuz Zannat ◽  
...  
Keyword(s):  
Molecular Docking ◽  
T Cell ◽  
Density Functional ◽  
Rational Design ◽  
Purine Nucleoside Phosphorylase ◽  
Parent Compound ◽  
Docking Studies ◽  
Purine Nucleoside ◽  
Nucleoside Phosphorylase ◽  
Acyclovir Derivatives

Purine nucleoside phosphorylase (PNP) is one of the major enzymes in the purine salvage pathway. It is responsible for the elevation of deoxyguanosine, and thus considered as the potent target in T-cell lymphoma. The present study examined acyclovir, reported as a low-affinity PNP inhibitor, for the rational design of new acyclovir derivatives by incorporating halogens, hydroxyl, and bulky amino groups. The molecular actions of designed derivatives were investigated by employing density functional theory, molecular docking, and binding energy calculations. The results revealed that the newly designed compounds were highly stable and showed more affinity to PNP than the parent compound, acyclovir. The quantum mechanics and molecular docking studies suggested that modification of side chains with bulky polar groups provided better binding affinities than substitutions with halogens. The resultant derivatives have strong polar interactions like His257 and Tyr88. Furthermore, the designed derivatives were within the ideal range of ADMET (absorption, distribution, metabolism, elimination, and toxicity) analysis. Considering that, these findings recommend further validation of designed acyclovir derivatives in wet lab confirmatory analysis with the emphasis on the further improvements in the treatment of T-cell-mediated diseases.

Inhibition of human purine nucleoside phosphorylase by tenofovir phosphate congeners

2010 ◽  
Vol 75 (12) ◽  
pp. 1249-1257 ◽  
Author(s):  
Ivan Votruba ◽  
Jana Trýznová ◽  
Petra Břehová ◽  
Eva Tloušťová ◽  
Květoslava Horská ◽  
...  
Keyword(s):  
Mixed Type ◽  
Purine Nucleoside Phosphorylase ◽  
Docking Studies ◽  
Purine Nucleoside ◽  
Nucleoside Phosphorylase ◽  
Purine Bases ◽  
Structure Activity ◽  
Derivatives Of

The structure-activity study on the phosphates of phosphonomethoxypropyl derivatives of purine bases interacting with human purine nucleoside phosphorylase has shown that the most efficient inhibitors of the enzyme are (R)- and (S)-PMPGp with Ki ~ 1.9 × 10–8 and/or 2.2 × 10–8 mol/l. The kinetic experiments have proven, with the exception of both enantiomers of PMP-8-BrDAPp, strictly competitive character of inhibition for all ANP monophosphates tested. Bromine derivatives exhibited uncompetitive and mixed type of inhibition as well. These results were confirmed by docking studies. The substitution of purine moiety with the bromine at the position 8 lead to an allosteric binding of these compounds toward the enzyme.

Molecular modeling and dynamics studies of purine nucleoside phosphorylase from Bacteroides fragilis

2009 ◽  
Vol 15 (8) ◽  
pp. 913-922
Author(s):  
Ivani Pauli ◽  
Luis Fernando Saraiva Macedo Timmers ◽  
Rafael Andrade Caceres ◽  
Luiz Augusto Basso ◽  
Diógenes Santiago Santos ◽  
...  
Keyword(s):  
Molecular Modeling ◽  
Purine Nucleoside Phosphorylase ◽  
Bacteroides Fragilis ◽  
Purine Nucleoside ◽  
Nucleoside Phosphorylase
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