Human serum albumin-drug acidic compounds

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.

Human serum albumin (HSA) is an important transporter of fatty acids, metabolites, drugs, and organic compounds in the circulatory system [93, 94], It is a single polypeptide chain consisting of 585 amino acids. Under physiological conditions (pH 7), HSA adopts a heart-shaped three-dimensional (3D) structure with three homologous domains I—III (Fig. 14) each domain contains two subdomains A and B, which consist of four and six a-helices, respectively [95, 96]. The X-ray structure shows that two halves of the albumin molecule... 

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 ).

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