Measurement of HSA-Drug Binding Affinity

Measurement of HSA-Drug Binding Affinity using Liquid Chromatography... 

The prediction of HSA-drug binding affinity is useful in the pharmaceutical industry to speed up the design of new compounds. The prediction of log A hsa was studied using log k values measured with an immobilized-HSA column. After an extensive QSAR analysis using 53 descriptors, an acceptable correlation was obtained using 12 descriptors. The following equation was then obtained ... 

Table 7.7 Molecular properties of some acidic compounds, logn represents the Human Serum Albumin (HSA)-drug binding affinity, from ref. 13. lognSf represents the HSA-drug binding affinity measured using a two-column system, from ref. 13. pKl are reference values, from ref. 13 TpKl values were measured by ion-exchange liquid chromatography. Mlm represents the molecular interaction eneigy calculated for the molecular-form compound, and Mlj the molecular interaction energy calculated for the ionic-form compound (kcal moP ).

Table 18 Human serum albumin-drug binding affinity and drug properties. rrSTi represents log k measured using an immobilized-HSA phase. nKa represents predicted log hsa-represents log k of acidic compounds at pH 7.4. k represents log k of basic compounds at pH 7.4. MIFa and MIFb represents the molecular interaction energy values of acidic and basic compounds, resepectively. nKs represents log nST measured using a modified Hummel-Dreyer method. nJQ, nKs, nSTg and nKj represent values. PB and PB2 represent the binding %. Log Pc are predicted log P values, and log Pm are measured values. 7.4 represents pH 7.4. Reproduced by permission of Bentham Science, ref. 20.

Desfosses et al. [328] measured binding of oxyphenyl betazone to the N-ter-minal peptic fragment of human serum albumin (HSA) in aqueous buffer and AOT/isooctane-RMs. The peptide affinity for the drug did not decrease in RMs. The interactions of HSA at membrane mimetic interface and its subsequent unfolding was suggested to constitute a drug release facilitating mechanism. 

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