Interactions drug-protein

TJ Mikkelson, SS Chrai, JR Robinson. (1973). Competitive inhibition of drug-protein interaction in the eye fluids and tissues. J Pharm Sci 62 1942-1945. 

Most experimental investigations have been concerned with measuring drug-protein interactions at equilibrium, and since the binding is a reversible process the law of mass action has been the basis upon which several equations have been developed for exploiting experimental data. 

DS Hage, SA Tweed. Recent advances in chromatographic and electrophoretic methods for the study of drug-protein interactions. J Chromatogr B 699 499-525, 1997. 

Another technique that has been used in CE format for chiral drug-protein interactions is the Hummel-Dreyer method (52). In this technique, the solute is dissolved in the run buffer at varying concentrations, creating a high detector background response. After equilibration of the system, mixtures of the ligand and protein in various ratios are injected into this system as a sample. 

The choice of the ACE method most suited for a given drug-protein interaction will therefore depend on several factors. Among them are inherent properties of the complexation, such as the estimated dissociation constant, the on/off-rates or multiple binding sites, as well as properties related to the behavior under ACE conditions, such as solubility, detectability, adsorption to the inner capillary wall, and mobility of all species under investigation. 

Since the polymeric serum proteins are inherently optically active, it follows that chiroptical behavior can be observed if the solute interacts with the protein in a stereoselective manner. A variety of studies have been performed in which the induced CD has been used to evaluate critical details of drug-protein interaction, and the early applications of these have been reviewed by Perrin and Hart [67]. When the chiroptical effects are sufficiently intense, the method may even be used to study the competitive binding of two drugs to a given protein system, thus providing data pertaining to the concurrent administration of these agents. 

We hypothesize that a subtle drug protein interaction occurs when polar solvents are used to extract highly lipid soluble drugs from plasma. These solvents are capable of delipidizing lipoproteins. It is possible that, when delipidization occurs, the hydro-phobic region of that protein is exposed. The hydro-phobic region could then bind A9-THC and the binding... 

Over recent years the realization that (i) most diseases are manifested at the protein level, (ii) therapeutic treatments primarily involve drug-protein interactions and (iii) there is often poor correlation between gene and protein expression has led to the development of the field of protein expression profiling—proteomics. The lack of correlation between gene and protein expression can be attributed to ... 

Drug-Protein Interaction by Affinity-Based HPLC/MS... 

Hudecz, F. and Szekerke, M. (1980) Investigation of drug-protein interactions and the drug-carrier concept by the use of branched polypeptides as model systems. Synthesis and characterization of the model peptides. Coll. Czech. Chem. Commun. 45, 933—940. 

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