<i>In silico</i> prediction of drug‐binding strengths to human serum albumin

Colmenarejo, Gonzalo

doi:10.1002/med.10039

Cited by 259 publications

(202 citation statements)

References 51 publications

Supporting

Mentioning

189

Contrasting

Order By: Relevance

“…It is also important to have the ability to estimate these in vitro properties from the chemical structure thus helping the design stage of the molecules too. It has been shown that the retention of compounds obtained on the proposed biomimetic stationary phases can be estimated in silico [52][53][54][55], however it is worth noting that the in silico models use 2D molecular descriptors that are not sufficient to estimate the 3D contribution of the molecules binding to proteins, therefore they can be used only as a rough estimations.…”

Section: Introductionmentioning

confidence: 99%

In vitro membrane binding and protein binding (IAM MB/PB technology) to estimate in vivo distribution: applications in early drug discovery

Valkó¹,

Teague²,

Pidgeon³

2017

ADMET DMPK

View full text Add to dashboard Cite

show abstract

Section: Introductionmentioning

confidence: 99%

In vitro membrane binding and protein binding (IAM MB/PB technology) to estimate in vivo distribution: applications in early drug discovery

Valkó¹,

Teague²,

Pidgeon³

2017

ADMET DMPK

View full text Add to dashboard Cite

show abstract

“…Three of the seven FA binding sites overlap with the two main drug binding sites, namely FA3 and FA4 overlap with site II, and FA7 with site I [8,12]. Therefore, competition between the drugs and FAs for the same binding sites is possible, although cooperativity, or even lack of competition have been observed in some cases [13].…”

Section: Interaction Of Anticancer Metallodrugs With Proteins Is Of Cmentioning

confidence: 99%

Investigation of the binding of cis/trans-[MCl4(1H-indazole)(NO)]− (M = Ru, Os) complexes to human serum albumin

Dömötör

Rathgeb

Kuhn

et al. 2016

Journal of Inorganic Biochemistry

View full text Add to dashboard Cite

Overall binding affinity of sodium or indazolium cis/trans-[MCl 4 (1H-indazole)(NO)] (M = Ru,Os) complexes towards human serum albumin (HSA) and high molecular mass components of the blood serum was monitored by ultrafiltration. HSA was found to be mainly responsible for the binding of the studied ruthenium and osmium complexes. In other words, this protein can provide a depot for the compounds and can affect their biodistribution and transport processes. In order to elucidate the HSA binding sites tryptophan fluorescence quenching studies and displacement reactions with the established site markers warfarin and dansylglycine were performed. Conditional stability constants for the binding to sites I and II on HSA were computed showing that the studied ruthenium and osmium complexes are able to bind into both sites with moderately strong affinity (logK' = 4.4-5.1). Site I is slightly more favored over site II for all complexes. No significant differences in the HSA binding properties were found for these metal complexes demonstrating negligible influence of the type of counter ion (sodium vs. indazolium), the metal ion center identity (Ru vs. Os) or the position of the nitrosyl group on the binding 2 event. Electron paramagnetic resonance spin labeling of HSA revealed that indazolium trans-[RuCl 4 (1H-indazole)(NO)] and long-chain fatty acids show competitive binding to HSA.Moreover, this complex has a higher affinity for site I, but when present in excess, it is able to bind to site II as well, and displace fatty acids.

show abstract

“…This would allow speeding up of the design of new compounds with appropriate BSA binding properties and therefore the optimization of the pharmacokinetics. This approach has been successfully utilized for the prediction of many physical properties, and it is one of the main approaches in the area of binding affinity prediction [18][19][20]. To the best of our knowledge, there are no QSPR studies focused on the prediction of the binding constants of active traditional Chinese medicine constituents measured by fluorescence quenching until now.…”

Section: Central European Journal Of Chemistrymentioning

confidence: 99%

Quantitative structure-property relationship study on the determination of binding constant by fluorescence quenching

et al. 2009

View full text Add to dashboard Cite

Models to predict binding constant (logK) to bovine serum albumin (BSA) should be very useful in the pharmaceutical industry to help speed up the design of new compounds, especially as far as pharmacokinetics is concerned. We present here an extensive list of logK binding constants for thirty-five compounds to BSA determined by florescence quenching from the literature. These data have allowed us the derivation of a quantitative structure-property relationship (QSPR) model to predict binding constants to BSA of compounds on the basis of their structure. A stepwise multiple linear regression (MLR) was performed to build the model. The statistical parameter provided by the MLR model (R = 0.9200, RMS = 0.3305) indicated satisfactory stability and predictive ability for the model. Using florescence quenching spectroscopy, we also experimentally determined the binding constants to BSA for two bioactive components in traditional Chinese medicines. Using the proposed model it was possible to predict the binding constants for each, which were in good agreement with the experimental results. This QSPR approach can contribute to a better understanding of structural factors of the compounds responsible for drug-protein interactions, and be useful in predicting the binding constants of other compounds.© Versita Warsaw and Springer-Verlag Berlin Heidelberg.

show abstract

In silico prediction of drug‐binding strengths to human serum albumin

Cited by 259 publications

References 51 publications

In vitro membrane binding and protein binding (IAM MB/PB technology) to estimate in vivo distribution: applications in early drug discovery

In vitro membrane binding and protein binding (IAM MB/PB technology) to estimate in vivo distribution: applications in early drug discovery

Investigation of the binding of cis/trans-[MCl4(1H-indazole)(NO)]− (M = Ru, Os) complexes to human serum albumin

Quantitative structure-property relationship study on the determination of binding constant by fluorescence quenching

Contact Info

Product

Resources

About