Low Molecular Mass Gelators of Organic Liquids and the Properties of Their Gels

About Supramolecular Assemblies of π-Conjugated Systems

Albumin as a drug carrier: design of prodrugs, drug conjugates and nanoparticles.

Structural Basis of the Drug-Binding Specificity of Human Serum Albumin.

Hydrogen Production by Molecular Photocatalysis

Human serum albumin (HSA) is an abundant plasma protein that binds a wide variety of hydrophobic ligands including fatty acids, bilirubin, thyroxine and hemin. Although HSA-heme complexes do not bind oxygen reversibly, it may be possible to develop modified HSA proteins or heme groups that will confer this ability on the complex. We present here the crystal structure of a ternary HSA-hemin-myristate complex, formed at a 1:1:4 molar ratio, that contains a single hemin group bound to subdomain IB and myristate bound at six sites. The complex displays a conformation that is intermediate between defatted HSA and HSA-fatty acid complexes; this is likely to be due to low myristate occupancy in the fatty acid binding sites that drive the conformational change. The hemin group is bound within a narrow D-shaped hydrophobic cavity which usually accommodates fatty acid; the hemin propionate groups are coordinated by a triad of basic residues at the pocket entrance. The iron atom in the centre of the hemin is coordinated by Tyr161. The structure of the HSA-hemin-myristate complex (PDB ID 1o9x) reveals the key polar and hydrophobic interactions that determine the hemin-binding specificity of HSA. The details of the hemin-binding environment of HSA provide a structural foundation for efforts to modify the protein and/or the heme molecule in order to engineer complexes that have favourable oxygen-binding properties.

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Crystal structural analysis of human serum albumin complexed with hemin and fatty acid.

Artificial oxygen carriers, hemoglobin vesicles and albumin-hemes, based on bioconjugate chemistry.

Solid nanotubes comprising alpha-Fe2O3 nanoparticles were prepared from iron-storage protein ferritin. Their structure, magnetic properties, and photocatalytic activities were characterized. The initial ferritin nanotube precursors were fabricated using alternating layer-by-layer depositions of poly-L-arginine (PLA) and ferritin into a track-etched polycarbonate membrane (pore diameter, 400 nm) with subsequent dissolution of the template. The obtained uniform cylinders of (PLA/ferritin)3 (outer diameter, 410 +/- 14 nm) were calcinated at 500 degrees C under air, yielding reddish-brown iron oxide nanotubes. The one-dimensional hollow structure remained perfect, but its diameter, wall thickness, and maximum length were markedly diminished. Disappearance of the protein shell and the PLA layers were confirmed using IR and EDX spectroscopy. Subsequent SEM, TEM, and XPS measurements showed that the tubular walls comprise fine alpha-Fe2O3 nanoparticles with a 5 nm diameter. These alpha-Fe2O3 nanotubes demonstrated superparamagnetic properties with a blocking temperature of 37 K and efficient photocatalytic activity for degradation of 4-chlorophenol.

Solid nanotubes comprising alpha-Fe2O3 nanoparticles prepared from ferritin protein.

Infectious hepatitis B virus (HBV), namely Dane particles (DPs), consists of a core nucleocapsid including genome DNA covered with an envelope of hepatitis B surface antigen (HBsAg). We report the synthesis, structure, and HBV-trapping capability of multilayered protein nanotubes having an anti-HBsAg antibody (HBsAb) layer as an internal wall. The nanotubes were prepared using an alternating layer-by-layer assembly of human serum albumin (HSA) and oppositely charged poly-l-arginine (PLA) into a nanoporous polycarbonate (PC) membrane (pore size, 400 nm), followed by depositions of poly-l-glutamic acid (PLG) and HBsAb. Subsequent dissolution of the PC template yielded (PLA/HSA)2PLA/PLG/HBsAb nanotubes (AbNTs). The SEM measurements revealed the formation of uniform hollow cylinders with a 414 ± 16 nm outer diameter and 59 ± 4 nm wall thickness. In an aqueous medium, the swelled nanotubes captured noninfectious spherical small particles of HBsAg (SPs); the binding constant was 3.5 × 107 M−1. Surprisingly, the...

Virus Trap in Human Serum Albumin Nanotube

This review presents highlights of our latest results of studies directed at developing protein-based smart nanotubes for biomedical applications. These practical biocylinders were prepared using an alternate layer-by-layer (LbL) assembly of protein and oppositely charged poly(amino acid) into a nanoporous polycarbonate (PC) membrane (pore diameter, 400 nm), with subsequent dissolution of the template. The tube wall typically comprises six layers of poly-L-arginine (PLA) and human serum albumin (HSA) [(PLA/HSA)3]. The obtained (PLA/HSA)3 nanotubes (NTs) can be dispersed in aqueous medium and are hydrated significantly. Several ligands for HSA, such as zinc(II) protoporphyrin IX (ZnPP), were bound to the HSA component in the cylindrical wall. Similar NTs comprising recombinant HSA mutant, which has a strong binding affinity for ZnPP, captured the ligand more tightly. The Fe3O4-coated NTs can be collected easily by exposure to a magnetic field. The hybrid NTs bearing a single avidin layer as an internal wall captured biotin-labeled nanoparticles into the central channel when their particle size is sufficiently small to enter the pores. The NTs with an antibody surface interior entrapped human hepatitis B virus with size selectivity. It is noteworthy that the infectious Dane particles were encapsulated completely into the hollows. Other HSA-based NTs having an α-glucosidase inner wall hydrolysed a glucopyranoside to yield α-D-glucose. A perspective of the practical use of the protein-based NTs is also described.

Teruyuki Komatsu

Papers

Crystal structural analysis of human serum albumin complexed with hemin and fatty acid.

Artificial oxygen carriers, hemoglobin vesicles and albumin-hemes, based on bioconjugate chemistry.

Solid nanotubes comprising alpha-Fe2O3 nanoparticles prepared from ferritin protein.

Virus Trap in Human Serum Albumin Nanotube

Protein-based nanotubes for biomedical applications