Human serum albumin

About: Human serum albumin is a research topic. Over the lifetime, 9402 publications have been published within this topic receiving 269029 citations. The topic is also known as: serum albumin & ALB.

The role of cisplatin and NAMI-A plasma-protein interactions in relation to combination therapy.

Abstract: The aim of the study is to evaluate the differences of protein binding of NAMI-A, a new ruthenium drug endowed with selective antimetastatic properties, and of cisplatin and to ascertain the possibility to use two drugs based on heavy metals in combination to treat solid tumor metastases. For this purpose, we have developed a technique that allows the proteins, to which metal drugs bind, to be identified from real protein mixts. Following incubation with the drugs, the bands contg. platinum and/or ruthenium are sepd. by native PAGE, SDS-PAGE and 2D gel electrophoresis, and identified using laser ablation inductively coupled plasma mass spectrometry. Both drugs interact with essentially the same proteins which, characterised by proteomics, are human serum albumin precursor, macroglobulin α 2 and human serotransferrin precursor. The interactions of NAMI-A are largely reversible whereas cisplatin forms stronger interactions that are less reversible. These data correlate well with the MCa mammary carcinoma model on which full doses of NAMI-A combined with cisplatin show additive effects as compared to each treatment taken alone, independently of whether NAMI-A precedes or follows cisplatin. Furthermore, the implication from this study is that the significantly lower toxicity of NAMI-A, compared to cisplatin, could be a consequence of differences in the mode of binding to plasma proteins, involving weaker interactions compared to cisplatin.

Discovery and optimization of anthranilic acid sulfonamides as inhibitors of methionine aminopeptidase-2: a structural basis for the reduction of albumin binding.

Abstract: Methionine aminopeptidase-2 (MetAP2) is a novel target for cancer therapy. As part of an effort to discover orally active reversible inhibitors of MetAP2, a series of anthranilic acid sulfonamides with micromolar affinities for human MetAP2 were identified using affinity selection by mass spectrometry (ASMS) screening. These micromolar hits were rapidly improved to nanomolar leads on the basis of insights from protein crystallography; however, the compounds displayed extensive binding to human serum albumin and had limited activity in cellular assays. Modifications based on structural information on the binding of lead compounds to both MetAP2 and domain III of albumin allowed the identification of compounds with significant improvements in both parameters, which showed good cellular activity in both proliferation and methionine processing assays.

Carboxybetaine polymer-protected gold nanoparticles: High dispersion stability and resistance against non-specific adsorption of proteins

Abstract: 1-Carboxy-N,N-dimethyl-N-(2'-methacryloyloxyethyl)methanaminium inner salt (CMB) was polymerized by ATRP initiated with a disulfide difunctionalized by 2-bromoisobutyryl groups. The disulfide-carrying carboxybetaine polymer (DT-PCMB) was used for the preparation of PCMB-protected gold nanoparticles (PCMB-AuNPs) obtained by the reduction of hydrogen tetrachloroaurate (HAuCl 4 ) in the presence of the DT-PCMB of different molecular weights at different molar ratios of DT-PCMB and HAuCl 4 . The sizes of gold cores in the PCMB-AuNPs tended to increase upon decreasing concentration and molecular weight of the DT-PCMB. The PCMB-AuNPs possessed a high dispersion stability, and showed a resistance against non-specific adsorption of proteins (bovine serum albumin, human serum albumin, lysozyme, and cytochrome c). Therefore, DT-PCMB is a quite suitable stabilizing ligand to prepare inert AuNPs and the PCMB-AuNPs will be useful in biomedical applications.