Dataset Information

Interactions Between Sirolimus and Anti-Inflammatory Drugs: Competitive Binding for Human Serum Albumin.

ABSTRACT: The aim of the present study was investigating the effects of three anti-inflammatory drugs, on Sirolimus protein biding. The binding site of Sirolimus on human serum albumin (HSA) was also determined.Six different concentrations of Sirolimus were separately exposed to HSA at pH 7.4 and 37°C. Ultrafiltration method was used for separating free drug; then free drug concentrations were measured by HPLC. Finally, Sirolimus protein binding parameters was calculated using Scatchard plots. The same processes were conducted in the presence of NSAIDs at lower concentration of albumin and different pH conditions. To characterize the binding site of Sirolimus on albumin, the free concentration of warfarin sodium and Diazepam, site I and II specific probes, bound to albumin were measured upon the addition of increasing Sirolimus concentrations.Based on the obtained results presence of Diclofenac, Piroxicam and Naproxen, could significantly decrease the percentage of Sirolimus protein binding. The Binding reduction was the most in the presence of Piroxicam. Sirolimus-NSAIDs interactions were increased in higher pH values and also in lower albumin concentrations. Probe displacement study showed that Sirolimus may mainly bind to site I on albumin molecule.More considerations in co-administration of NSAIDs and Sirolimus is recommended.

SUBMITTER: Khodaei A

PROVIDER: S-EPMC4961981 | biostudies-other | 2016 Jun

REPOSITORIES: biostudies-other

ACCESS DATA

Publications

Interactions Between Sirolimus and Anti-Inflammatory Drugs: Competitive Binding for Human Serum Albumin.

Khodaei Arash A Bolandnazar Soheila S Valizadeh Hadi H Hasani Leila L Zakeri-Milani Parvin P

Advanced pharmaceutical bulletin 20160630 2

<h4>Purpose</h4>The aim of the present study was investigating the effects of three anti-inflammatory drugs, on Sirolimus protein biding. The binding site of Sirolimus on human serum albumin (HSA) was also determined.<h4>Methods</h4>Six different concentrations of Sirolimus were separately exposed to HSA at pH 7.4 and 37°C. Ultrafiltration method was used for separating free drug; then free drug concentrations were measured by HPLC. Finally, Sirolimus protein binding parameters was calculated us ...[more]

PMID: 27478785

Similar Datasets

Project description:Protein structure can be flexible to adopt multiple conformations to house small molecules. In this paper, we have attempted to experimentally figure out how the structure of a transport protein steer the drug-drug competition (DDC) by maintaining the equilibrium distribution of the bound and unbound fractions of drugs. This understanding is an important facet in biophysical and medicinal chemistry to ascertain the effectiveness of drugs. It is important to note that majority of studies involving small-molecule-transport protein interaction aimed at characterizing the binding process, and because these proteins can interact with thousands of molecules, there are hundreds of reports on such interactions. This ultimately led to an impression among the readers that any studies involving serum albumin may not lead to any new findings except for traditional binding explorations. However, in the present paper, we would like to draw the attention of the readers that our findings are very surprising, new, and important, involving the phenomenon of ligand-protein interaction. Here, we have studied two structurally similar drugs methotrexate (MTX) and folic acid (FA), which attempt to bind the primary binding site (subdomain IIA), one at a time, of human serum albumin. Details of binding analyses reveal that when both of the drugs are present, the single-site binding mode of FA prefers to occupy the primary binding site and hence pushes the primary-site-bound MTX to another location (subdomain IIIA), which is the second binding site of MTX. The structural analysis indicates that DDC has occurred in a cooperative fashion so that the loss of the protein secondary structure is minimum when both drugs are bound to the protein, which means that in the case of duo-drug binding, the conventional interaction between the drug and the protein is altered to undergo restoration of the protein structure. This can indeed regulate the DDC by modifying the bound and unbound fractions of MTX in plasma. The present study emphasizes that in vitro structural characterizations of the transport protein provide important information to improve the molecular-level understanding of DDC for further therapeutic applications with combination drug.

Dataset Information

Interactions Between Sirolimus and Anti-Inflammatory Drugs: Competitive Binding for Human Serum Albumin.

Publications

Interactions Between Sirolimus and Anti-Inflammatory Drugs: Competitive Binding for Human Serum Albumin.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets