Unraveling the binding interaction and kinetics of a prospective anti-HIV drug with a model transport protein: results and challenges

2013 ◽  
Vol 15 (4) ◽  
pp. 1275-1287 ◽  
Author(s):  
Bijan Kumar Paul ◽  
Debarati Ray ◽  
Nikhil Guchhait
Keyword(s):  
Transport Protein ◽  
Binding Interaction ◽  
Kinetics Of ◽  
Anti Hiv

Inhibition of the chlorinating activity of myeloperoxidase by tempol: revisiting the kinetics and mechanisms

2011 ◽  
Vol 439 (3) ◽  
pp. 423-434 ◽  
Author(s):  
Raphael F. Queiroz ◽  
Sandra M. Vaz ◽  
Ohara Augusto
Keyword(s):  
Hypochlorous Acid ◽  
Tissue Injury ◽  
Kinetic Modelling ◽  
Oxidation Kinetic ◽  
Reversible Inhibitor ◽  
Binding Interaction ◽  
Oxidative Potential ◽  
Oxidant Production ◽  
A Minor ◽  
Kinetics Of

The nitroxide tempol (4-hydroxy-2,2,6,6-tetramethyl piperidine-1-oxyl) reduces tissue injury in animal models of inflammation by mechanisms that are not completely understood. MPO (myeloperoxidase), which plays a fundamental role in oxidant production by neutrophils, is an important target for anti-inflammatory action. By amplifying the oxidative potential of H2O2, MPO produces hypochlorous acid and radicals through the oxidizing intermediates MPO-I [MPO-porphyrin•+-Fe(IV)=O] and MPO-II [MPO-porphyrin-Fe(IV)=O]. Previously, we reported that tempol reacts with MPO-I and MPO-II with second-order rate constants similar to those of tyrosine. However, we noticed that tempol inhibits the chlorinating activity of MPO, in contrast with tyrosine. Thus we studied the inhibition of MPO-mediated taurine chlorination by tempol at pH 7.4 and re-determined the kinetic constants of the reactions of tempol with MPO-I (k=3.5×105 M−1·s−1) and MPO-II, the kinetics of which indicated a binding interaction (K=2.0×10−5 M; k=3.6×10−2 s−1). Also, we showed that tempol reacts extremely slowly with hypochlorous acid (k=0.29 and 0.054 M−1·s−1 at pH 5.4 and 7.4 respectively). The results demonstrated that tempol acts mostly as a reversible inhibitor of MPO by trapping it as MPO-II and the MPO-II–tempol complex, which are not within the chlorinating cycle. After turnover, a minor fraction of MPO is irreversibly inactivated, probably due to its reaction with the oxammonium cation resulting from tempol oxidation. Kinetic modelling indicated that taurine reacts with enzyme-bound hypochlorous acid. Our investigation complements a comprehensive study reported while the present study was underway [Rees, Bottle, Fairfull-Smith, Malle, Whitelock and Davies (2009) Biochem. J. 421, 79–86].

Binding interaction of potent HIV-1 NNRTIs, amino-oxy-diarylquinoline with the transport protein using spectroscopic and molecular docking

2020 ◽  
Vol 233 ◽  
pp. 118159
Author(s):  
Suwicha Patnin ◽  
Arthit Makarasen ◽  
Mayuso Kuno ◽  
Sirinya Deeyohe ◽  
Supanna Techasakul ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Transport Protein ◽  
Binding Interaction ◽  
Hiv 1

Design and Cellular Kinetics of Dansyl-labeled CADA Derivatives with Specific Anti-HIV and CD4 Receptor Down-modulating Properties

2007 ◽  
Vol 74 (3) ◽  
pp. A68-A69
Author(s):  
K VERMEIRE ◽  
A LISCO ◽  
J GRIVEL ◽  
P BLANK ◽  
V SCHRAM ◽  
...  
Keyword(s):  
Cellular Kinetics ◽  
Cd4 Receptor ◽  
Kinetics Of ◽  
Anti Hiv

scholarly journals Stoichiometry of a half-turnover of band 3, the chloride transport protein of human erythrocytes.

1982 ◽  
Vol 79 (2) ◽  
pp. 169-185 ◽  
Author(s):  
M L Jennings
Keyword(s):  
Chloride Transport ◽  
Band 3 ◽  
Transport Protein ◽  
Red Cell ◽  
Rapid Loss ◽  
Inhibitory Potency ◽  
Transport Cycle ◽  
Nonequilibrium Conditions ◽  
Kinetics Of ◽  
Phosphate Medium

The kinetics of human red blood cell Cl transport have been studied under nonequilibrium conditions to determine whether or not an outward Cl gradient can recruit the transport protein from an inward-facing to an outward-facing configuration. Three kinds of evidence are consistent with this outward recruitment. First, the initial net Cl efflux into a Cl-free phosphate medium is independent of the intracellular Cl concentration in the range 20-170 mM. Second, an outward Cl gradient strongly enhances the inhibitory potency of DNDS (4,4'-dinitro-2,2'-stilbene disulfonate), which suggests that DNDS binds primarily to outward-facing states. Finally, we have estimated the number of Cl ions transported during the putative outward recruitment. Resealed red cell ghosts containing only 70 muM 36Cl were resuspended at 0 degrees C in a Cl-free, HCO3-free Na2SO4 medium. In the first 10 s, or approximately 10(6) Cl ions per ghost, followed by a much slower further loss of Cl. The rapid loss of 10(6) Cl ions per ghost, which is abolished by pretreatment with DIDS (4,4'-diisothiocyano-2,2'-stilbene disulfonate), appears to represent the Cl that is transported during the first half-turnover of the transport cycle. These data are strong evidence that the influx and efflux events in the catalytic cycle for anion transport do not take place simultaneously, and that the stoichiometry of the transport cycle is close to one pair of anions exchanged per band 3 monomer.

Kinetics of the hydrolysis of 2′,3′-dideoxyguanosine: a potent anti-HIV agent

1991 ◽  
Vol 73 (2) ◽  
pp. 105-110 ◽  
Author(s):  
A. Van Schepdael ◽  
N. Ossembe ◽  
L. Jie ◽  
P. Herdewijn ◽  
E. Roets ◽  
...  
Keyword(s):  
Kinetics Of ◽  
Hydrolysis Of ◽  
Anti Hiv

Antihypertensive activity of a quinoline appended chalcone derivative and its site specific binding interaction with a relevant target carrier protein

RSC Advances ◽  
2015 ◽  
Vol 5 (80) ◽  
pp. 65496-65513 ◽  
Author(s):  
Himank Kumar ◽  
Vinod Devaraji ◽  
Ritika Joshi ◽  
Manojkumar Jadhao ◽  
Piyush Ahirkar ◽  
...  
Keyword(s):  
Therapeutic Target ◽  
Specific Binding ◽  
Transport Protein ◽  
Clear Picture ◽  
Antihypertensive Activity ◽  
Carrier Protein ◽  
Binding Interaction ◽  
Site Specific ◽  
Chalcone Derivative ◽  
Delivery Mechanism

The usefulness of heterocyclic chalcone derivative as a therapeutic target in controlling hypertension and its site specific binding interaction with model transport protein to get a clear picture about its delivery mechanism.

Simple and rapid determination of the enzyme kinetics of HIV-1 reverse transcriptase and anti-HIV-1 agents by a fluorescence based method

2011 ◽  
Vol 171 (2) ◽  
pp. 381-387 ◽  
Author(s):  
Kun Silprasit ◽  
Ratsupa Thammaporn ◽  
Supanna Tecchasakul ◽  
Supa Hannongbua ◽  
Kiattawee Choowongkomon
Keyword(s):  
Reverse Transcriptase ◽  
Enzyme Kinetics ◽  
Rapid Determination ◽  
Kinetics Of ◽  
Anti Hiv ◽  
Hiv 1
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