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ABSTRACT: A branched iron-phenanthroline based coordination polymer has been constructed in a water based system using a click chemistry approach to link monomeric coordination complexes together within a protein cage nanoarchitecture, which acts both as a template and a sized constrained reaction environment.
Chemical Communications 01/2010; 46(2):264-6. · 6.17 Impact Factor
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ABSTRACT: A DTPA-Gd containing polymer was grown in the interior of a heat shock protein cage resulting in T(1) particle relaxivities of 4200 mM(-1) sec(-1) for the 12 nm particle. Relaxivity parameters were determined, and this analysis suggests that the rotational correlation time has been optimized while the water exchange lifetime is longer than optimal. This synthetic approach holds much promise for the development of next generation contrast agents and this report will aid in their design.
Nano Letters 11/2009; 9(12):4520-6. · 13.20 Impact Factor
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ABSTRACT: A goal of biomimetic chemistry is to use the hierarchical architecture inherent in biological systems to guide the synthesis of functional three-dimensional structures. Viruses and other highly symmetrical protein cage architectures provide defined scaffolds to initiate hierarchical structure assembly. Here we demonstrate that a cross-linked branched polymer can be initiated and synthesized within the interior cavity of a protein cage architecture. Creating this polymer network allows for the spatial control of pendant reactive sites and dramatically increases the stability of the cage architecture. This material was generated by the sequential coupling of multifunctional monomers using click chemistry to create a branched cross-linked polymer network. Analysis of polymer growth by mass spectrometry demonstrated that the polymer was initiated at the interior surface of the cage at genetically introduced cysteine reactive sites. The polymer grew as expected to generation 2.5 where it was limited by the size constraints of the cavity. The polymer network was fully cross-linked across protein subunits that make up the cage and extended the thermal stability for the cage to at least 120 degrees C. The introduced reactive centers were shown to be active and their number density increased with increasing generation. This synthetic approach provides a new avenue for creating defined polymer networks, spatially constrained by a biological template.
Journal of the American Chemical Society 05/2009; 131(12):4346-54. · 9.91 Impact Factor
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Hideto Yonekura,
Yasuhiko Yamamoto,
Shigeru Sakurai,
Ralica G Petrova, Md Joynal Abedin,
Hui Li,
Kiyoshi Yasui,
Masayoshi Takeuchi,
Zenji Makita,
Shin Takasawa,
Hiroshi Okamoto,
Takuo Watanabe,
Hiroshi Yamamoto
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ABSTRACT: The binding of advanced glycation end-products (AGE) to the receptor for AGE (RAGE) is known to deteriorate various cell functions and is implicated in the pathogenesis of diabetic vascular complications. In the present study, we show that the cellular constituents of small vessels, endothelial cells (EC) and pericytes express novel splice variants of RAGE mRNA coding for the isoforms that lack the N-terminal V-type immunoglobulin-like domain (N-truncated) or the C-terminal transmembrane domain (C-truncated), as well as the known full-length mRNA. The ratio of the expression of the three variants was different between EC and pericytes; the content of the C-truncated form was highest in EC, whereas the full-length form was the most abundant in pericytes. Transfection experiments with COS-7 cells demonstrated that those variant mRNAs were translated into proteins as deduced; C-truncated RAGE was efficiently secreted into the culture media, and N-truncated RAGE was located mainly on the plasma membrane. The three isoforms were also detected in primary cultured human EC and pericytes. Further, full-length and C-truncated forms of RAGE bound to an AGE-conjugated column, whereas N-truncated RAGE did not. The AGE induction of extracellular-signal-related kinase phosphorylation and vascular endothelial growth factor in EC and of the growth and cord-like structure formation of EC was abolished completely by C-truncated RAGE, indicating that this endogenous secretory receptor (endogenous secretory RAGE) is cytoprotective against AGE. The results may contribute to our understanding of the molecular basis for the diversity of cellular responses to AGE and for individual variations in the susceptibility to diabetic vascular complications.
Biochemical Journal 04/2003; 370(Pt 3):1097-109. · 4.90 Impact Factor
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Hideto Yonekura,
Shigeru Sakurai,
Xiaoxu Liu,
Hideyuki Migita,
Hua Wang,
Sho-ichi Yamagishi,
Motohiro Nomura, Md. Joynal Abedin,
Hiroyuki Unoki,
Yasuhiko Yamamoto,
Hiroshi Yamamoto
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ABSTRACT: We have shown previously that vascular endothelial growth factor (VEGF) synthesized by the cellular constituents of small
vessels per se, viz.endothelial cells and pericytes, participates in the hypoxia-driven proliferation of both cell types (Nomura, M., Yamagishi,
S., Harada, S., Hayashi, Y., Yamashima, T., Yamashita, J., Yamamoto, H. (1995)J. Biol. Chem. 270, 28316–28324; Yamagishi, S., Yonekura, H., Yamamoto, Y., Fujimori, H., Sakurai, S., Tanaka, N., and Yamamoto, H. (1999)
Lab. Invest. 79, 501–509). In this study, we examined the expression of the recently isolated VEGF gene family members (placenta growth
factor (PlGF), VEGF-B, and VEGF-C) in human dermal microvascular endothelial cells and bovine retinal pericytes cultured under
various oxygen tensions. Quantitative reverse transcription-polymerase chain reaction analyses demonstrated that the two cell
types possess not only VEGF (VEGF-A) mRNA, but also VEGF-B, VEGF-C, and PlGF mRNAs. Among them, only VEGF-A mRNA was induced
under hypoxia. Competitive reverse transcription-polymerase chain reaction showed that, under normoxic conditions, the rank
order of mRNA content in endothelial cells was PlGF > VEGF-B > VEGF-C > VEGF-A and that mRNA coding for PlGF was expressed
at >100-fold higher levels than VEGF-A mRNA. In pericytes, the rank order was VEGF-C > VEGF-A > VEGF-B > PlGF, and ∼7-fold
higher levels of VEGF-C mRNA compared with VEGF-A mRNA were noted in this cell type. Furthermore, antisense inhibition of
PlGF protein production lowered the endothelial cell synthesis of DNA under hypoxic conditions. The results suggest that these
VEGF family members may also take active parts in angiogenesis.
Journal of Biological Chemistry 12/1999; 274(49):35172-35178. · 4.77 Impact Factor
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Nucleic Acids Research. 01/1999; 27:2591-2600.
