Role of tyrosine and tryptophan in chemically modified serum albumin on its tissue distribution.

To investigate the effect of functional groups in bovine serum albumin (BSA) on its tissue distribution characteristics, tyrosine (Tyr) or tryptophan (Trp) residues of BSA were chemically modified by tetranitromethane (TNM) and 2-hydroxy-5-nitrobenzyl bromide (HNB), respectively. BSA was successfully modified with each reagent depending on the amount of the reagent added to the reaction mixture, and TNM- and HNB-modified BSA derivatives with different degrees of modification were obtained. Circular dichroism measurements showed that slight secondary and large tertiary changes were detectable as the degree of modification increased.

Liver targeting of catalase by cationization for prevention of acute liver failure in mice.

To achieve hepatic delivery of CAT for the prevention of CCl4-induced acute liver failure in mice, two types of cationized CAT derivatives, HMD- and ED-conjugated CAT, were developed. Slight structural changes occurred during cationization and the number of increased free amino groups was 3.1 in HMD-CAT and 13.

Hydrolysis of angiotensin II receptor blocker prodrug olmesartan medoxomil by human serum albumin and identification of its catalytic active sites.

In the present study, we investigated the esterase-like activity of human serum albumin (HSA) and the mechanism by which it hydrolyzes, and thereby activates, olmesartan medoxomil (CS-866), a novel angiotensin II receptor antagonist. CS-866 has previously been shown to be rapidly hydrolyzed in serum in which HSA appeared to play the most important role in catalyzing the hydrolysis. We found that the hydrolysis of CS-866 by HSA followed Michaelis-Menten kinetics.

Cationic charge-dependent hepatic delivery of amidated serum albumin.

To obtain a quantitative correlation between the physicochemical properties of amidated bovine serum albumin (BSA) and their tissue distribution characteristics for the development of targeted delivery of proteins, BSA was amidated with hexamethylenediamine (HMD) or ethylenediamine (ED) to obtain cationized BSAs. Their structural changes were examined by spectroscopic and electrophoretic techniques then their tissue distribution was studied in mice. Circular dichroism (CD) and fluorescence measurements showed that spectroscopic changes occurred as the number of free NH2 groups increased.

Physicochemical, tissue distribution, and vasodilation characteristics of nitrosated serum albumin: delivery of nitric oxide in vivo.

Conjugates of nitric oxide (NO) to serum albumins are candidates for controlled delivery of NO in vivo, but their physicochemical and tissue distribution characteristics have hardly been examined yet. In this study, to achieve its in vivo delivery, bovine serum albumin (BSA) was reacted with sodium nitrite to obtain NO-BSA, which had 0.25-0.

Esterase-like activity of serum albumin: characterization of its structural chemistry using p-nitrophenyl esters as substrates.

Purpose: To elucidate the catalytic mechanism of the esterase-like activity of serum albumin (SA), the reactivity of SA from six species was investigated using p-nitrophenyl esters as model substrates.

Methods: The effect of pH and the energetic and thermodynamic profiles of SA were determined for all species for p-nitrophenyl acetate (PNPA). Then, kinetic and thermodynamic studies using a series of p- and o-nitrophenyl esters with different side chains and human SA (HSA) were carried out.

Stability of a cisplatin-chondroitin sulfate A complex in plasma and kidney in terms of protein binding.

To assess the stability of a cisplatin (CDDP) complex prepared with chondroitin sulfate A (CSA) relative to protein binding in the circulation and kidney, a trichloroacetic acid (TCA) precipitation method was developed to measure the protein-unbound species of CDDP and the CDDP-CSA complex in plasma and kidney homogenates. The total and unbound drug concentrations were determined up to 3 h following a 2 mg/kg bolus injection of CDDP or CDDP-CSA complex to rats. The stability against plasma binding was evaluated by a determination of the area under concentration-time curve from time 0 to infinite time (AUC(0-infinity)); the ratio of unbound drug AUC(0-infinity) to total drug AUC(0-infinity) was employed to estimate the availability of the unbound drug in the circulation.