scholarly journals Competitive binding interaction between Zn2+ and saxitoxin in cardiac Na+ channels. Evidence for a sulfhydryl group in the Zn2+/saxitoxin binding site

1991 ◽  
Vol 59 (3) ◽  
pp. 523-537 ◽  
Author(s):  
L. Schild ◽  
E. Moczydlowski
Keyword(s):  
Binding Site ◽  
Sulfhydryl Group ◽  
Competitive Binding ◽  
Na Channels ◽  
Binding Interaction

Is there a second external lidocaine binding site on mammalian cardiac cells?

1989 ◽  
Vol 257 (1) ◽  
pp. H79-H84 ◽  
Author(s):  
L. A. Alpert ◽  
H. A. Fozzard ◽  
D. A. Hanck ◽  
J. C. Makielski
Keyword(s):  
Binding Site ◽  
Cardiac Arrhythmias ◽  
Local Anesthetics ◽  
Sodium Current ◽  
Cardiac Cells ◽  
Na Channel ◽  
Functional Difference ◽  
Na Channels ◽  
Internal Perfusion ◽  
Cardiac Purkinje Cells

Lidocaine and its permanently charged analogue QX-314 block sodium current (INa) in nerve, and by this mechanism, lidocaine produces local anesthesia. When administered clinically, lidocaine prevents cardiac arrhythmias. Nerve and skeletal muscle are much more sensitive to local anesthetics when the drugs are applied inside the cell, indicating that the binding site for local anesthetics is located on the inside of those Na channels. Using a large suction pipette for voltage clamp and internal perfusion of single cardiac Purkinje cells, we demonstrate that a charged lidocaine analogue blocks INa not only when applied from the inside but also from the outside, unlike noncardiac tissue. This functional difference in heart predicts that a second local anesthetic binding site exists outside or near the outside of cardiac Na channels and emphasizes that the cardiac Na channel is different from that in nerve.

MODELING THE CONCENTRATIONS AND EFFICIENCIES FOR THE INTERACTING SPECIES OF PYROPHEOPHORBIDE METHYL ESTER-COPPER ASSOCIATION

2013 ◽  
Vol 08 (01n02) ◽  
pp. 73-87 ◽  
Author(s):  
S. AL-OMARI
Keyword(s):  
Methyl Ester ◽  
Fluorescence Quenching ◽  
Binding Site ◽  
Binding Constant ◽  
Pharmacokinetics And Pharmacodynamics ◽  
Dynamic Binding ◽  
Binding Interaction ◽  
Interacting Species ◽  
Different Temperatures ◽  
Dynamic Fluorescence

The interaction between pyropheophorbide methyl ester (PPME) and Cu 2+ was investigated using UV-vis and fluorescence spectrscopy. Study of the binding interaction between PPME and Cu 2+ could contribute to understanding of its pharmacokinetics and pharmacodynamics. Parameters of the static and dynamic fluorescence quenching of PPME- Cu 2+ association were calculated at different temperatures. For binding site of 1:1 at 299 K, the static binding constant (kS), the static isosbestic concentration ([Formula: see text]), the dynamic binding constant (kD), and the dynamic isosbestic concentration ([Formula: see text]) are, respectively, 61 M-1, 0.0164 M, 75 M-1, and 0.0133 M. The concentrations and efficiencies of the intermediates species were modeled. Satisfactory correspondence between the experimental and calculated results was found.

scholarly journals New Multi-Targeted Antiproliferative Agents: Design and Synthesis of IC261-Based Oxindoles as Potential Tubulin, CK1 and EGFR Inhibitors

2021 ◽  
Vol 14 (11) ◽  
pp. 1114
Author(s):  
Momen R. Fareed ◽  
Mai E. Shoman ◽  
Mohammed I. A. Hamed ◽  
Mohamed Badr ◽  
Hanin A. Bogari ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Colon Cancer ◽  
Binding Site ◽  
Microtubule Assembly ◽  
Experimental Result ◽  
G1 Phase ◽  
Mechanistic Study ◽  
Interaction Patterns ◽  
Binding Interaction ◽  
Colchicine Binding Site

A series of 3-benzylideneindolin-2-one compounds was designed and synthesized based on combretastatin A-4 and compound IC261, a dual casein kinase (CK1)/tubulin polymerization inhibitor, taking into consideration the pharmacophore required for EGFR-tyrosine kinase inhibition. The new molecular entities provoked significant growth inhibition against PC-3, MCF-7 and COLO-205 at a 10 μM dose. Compounds 6-chloro-3-(2,4,6-trimethoxybenzylidene) indolin-2-one, 4b, and 5-methoxy-3-(2,4,6-trimethoxybenzylidene)indolin-2-one, 4e, showed potent activity against the colon cancer COLO-205 cell line with an IC50 value of 0.2 and 0.3 μM. A mechanistic study demonstrated 4b’s efficacy in inhibiting microtubule assembly (IC50 = 1.66 ± 0.08 μM) with potential binding to the colchicine binding site (docking study). With an IC50 of 1.92 ± 0.09 μg/mL, 4b inhibited CK1 almost as well as IC261. Additionally, 4b and 4e were effective inhibitors of EGFR-TK with IC50s of 0.19 μg/mL and 0.40 μg/mL compared to Gifitinib (IC50 = 0.05 μg/mL). Apoptosis was induced in COLO-205 cells treated with 4b, with apoptotic markers dysregulated. Caspase 3 levels were elevated to more than three-fold, while Cytochrome C levels were doubled. The cell cycle was arrested in the pre-G1 phase with extensive cellular accumulation in the pre-G1 phase, confirming apoptosis induction. Levels of cell cycle regulating proteins BAX and Bcl-2 were also defective. The binding interaction patterns of these compounds at the colchicine binding site of tubulin and the Gifitinib binding site of EGFR were verified by molecular docking, which adequately matched the reported experimental result. Hence, 4b and 4e are considered promising potent multitarget agents against colon cancer that require optimization.

Competitive Binding Among Oral Streptococci to Hydroxyapatite

1977 ◽  
Vol 56 (2) ◽  
pp. 157-165 ◽  
Author(s):  
W.F. Liljemark ◽  
S.V. Schauer
Keyword(s):  
Binding Site ◽  
Streptococcus Mutans ◽  
Binding Sites ◽  
Competitive Binding ◽  
Oral Streptococci ◽  
Ha Coating ◽  
Relative Affinity

The relative affinity of various oral streptococci for hydroxyapatite (HA) differed widely. Streptococcus mutans affinity for dextran-coated HA was the highest of all the streptococci to any HA coating. S salivarius had the lowest affinity, and S sanguis affinity was higher than S miteor for saliva-coated HA. Competition for binding sites on saliva-coated, dextran-coated, and saliva-dextran-coated HA among these streptococci was not observed in any pair of these bacteria on any HA coating except for that of S miteor and S sanguis to saliva-coated HA. However, competition between this pair was not for the same binding site but for closely associated sites.

scholarly journals IN SILICO STUDY OF APIGENIN AND APIGETRIN AS INHIBITOR OF 3-HYDROXY-3-METHYL-GLUTAYL-COENZYME A REDUCTASE

2017 ◽  
Vol 10 (11) ◽  
pp. 284
Author(s):  
Dwintha Lestari ◽  
Elin Yulinah Sukandar ◽  
Irda Fidrianny
Keyword(s):  
Binding Site ◽  
Binding Affinity ◽  
In Silico ◽  
Coenzyme A ◽  
Inhibition Constant ◽  
Two Dimensional ◽  
Binding Interaction ◽  
Docking Result ◽  
Binding Process ◽  
In Silico Study

  Objective: The objectives of this research were to investigate in silico interaction between apigenin and apigetrin with 3-hydroxy-3-methyl-glutayl-coenzyme A (HMG Co-A) reductase, to find the most favorable binding site as well as to predict the binding mode.Materials and Methods: Docking calculation was performed by branded Sony Vaio PC Linux Ubuntu 14.04 LTS. The binding process based on the best docking result with HMG Co-A reductase was presented in two-dimensional diagram. Statin, atorvastatin, and R-mevalonate were used as standard.Results: Binding affinity and inhibition constant of R-mevalonate were Ei=−4.2 kcal/mol, Ki=836.78 μM; apigenin Ei=−7.0 kcal/mol, Ki=7.43 μM; apigetrin Ei=−5.9 kcal/mol, Ki=47.53 μM; simvastatin Ei=−8.2 kcal/mol; Ki=0.98 μM; atorvastatin Ei=−8.4 kcal/mol; Ki=0.7 μM. Apigenin had better binding interaction than apigetrin.Conclusion: Apigenin could be developed as anticholesterol.

scholarly journals The saxitoxin/tetrodotoxin binding site on cloned rat brain IIa Na channels is in the transmembrane electric field

1994 ◽  
Vol 67 (3) ◽  
pp. 1007-1014 ◽  
Author(s):  
J. Satin ◽  
J.T. Limberis ◽  
J.W. Kyle ◽  
R.B. Rogart ◽  
H.A. Fozzard
Keyword(s):  
Electric Field ◽  
Binding Site ◽  
Rat Brain ◽  
Na Channels

scholarly journals Evidences for a Sulfhydryl Group in the ATP-Binding Site of (Na+ + K+)-Activated ATPase

1975 ◽  
Vol 53 (1) ◽  
pp. 301-311 ◽  
Author(s):  
Rosemarie PATZELT-WENCZLER ◽  
Hartmut PAULS ◽  
Erland ERDMANN ◽  
Wilhelm SCHONER
Keyword(s):  
Binding Site ◽  
Sulfhydryl Group ◽  
Atp Binding ◽  
Atp Binding Site

An investigation of the destruction of the β-lactam ring of penems by the albumin drug-binding site

1981 ◽  
Vol 59 (10) ◽  
pp. 857-866 ◽  
Author(s):  
H. Bruderlein ◽  
R. Daniel ◽  
D. Perras ◽  
A. DiPaola ◽  
A. Fidelia ◽  
...  
Keyword(s):  
Binding Site ◽  
Plasma Proteins ◽  
Serum Proteins ◽  
Wide Spectrum ◽  
Sulfhydryl Group ◽  
Drug Binding ◽  
Exact Nature ◽  
Rat Serum ◽  
Sephadex Column ◽  
Drug Binding Site

The plasma proteins have been reported to exert irreversible effects on some β-lactams. The penems represent a class of antibiotics of great interest due to their wide spectrum of activity. However, many compounds of this class were found to be unstable in rat serum. A prototype compound, (±)-2-methylpenem-3-carboxylic acid (BCL-98), was selected for detailed investigations. The capacity of penems to inhibit the destruction of a chromogenic β-lactam (BCL-604) by serum was the technique selected to study the interaction of BCL-98 with serum proteins at the specific destructive site. The serum of various species was investigated and the magnitude of BCL-604 destruction was in the following order: rat = human > dog > mice. The human plasma proteins were fractionated on a Sephadex column and the fractions tested individually. The albumin fraction was found to be entirely responsible for the destruction, the globulin fractions being completely inactive. The reaction of Ellman's reagent with serum was not diminished in the presence of the BCL-98, thus demonstrating that the sulfhydryl group of albumin is not involved in this binding. Displacement of a fluorescent probe (5-dimethylaminonaphthalene-1-sulfonamide) by BCL-98 showed that the binding site for the latter is the same as the one occupied by L-tryptophan and thus involves the ε-lysine amino group of the albumin binding site. The exact nature of this binding is not yet established, but it can be inferred that it may involve acylation of the ε-lysine group at the binding site. Some analogs of BCL-98 were also investigated. The basic functionality seems to protect the molecule from the destructive site of the albumin, probably because this substituent induces binding at another nondestructive site resulting in a prolonged half-life in the blood.

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