C−H versus C−C Activation of Biphenylene in Its Reactions with Iron Group Carbonyl Clusters

Yeh, Wen-Yann; Hsu, Sodio C. N.; Peng, Shie‐Ming; Lee, Gene‐Hsiang

doi:10.1021/om9800445

Cited by 49 publications

(45 citation statements)

References 41 publications

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“…The hydrogen bond formation constrains the conformational flexibility of the RGD loop and may contribute to the lower binding affinity of the molecule and to the dissociable nature of the interaction with ␣ v ␤ 3 receptor. These observations are in agreement with the studies done on accutin, another member of the short disintegrin family (31). Accutin, which naturally contains Leu at the position of Met 28 within echistatin, inhibits angiogenesis in vivo and in vitro by blocking integrin ␣ v ␤ 3 of endothelial cells and by inducing apoptosis.…”

Section: Table I the Effect Of Recombinant Echistatin Eristostatin supporting

confidence: 91%

Structural Requirements of Echistatin for the Recognition of αvβ3 and α5β1Integrins

Wierzbicka-Patynowski¹,

Niewiarowski²,

Marcinkiewicz³

et al. 1999

Journal of Biological Chemistry

134

123

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There are key differences between the amino acid residues of the RGD loops and the C termini of echistatin, a potent antagonist of ␣ IIb ␤ 3 , ␣ v ␤ 3 and ␣ 5 ␤ 1 , and eristostatin, a similar disintegrin selectively inhibiting ␣ IIb ␤ 3 . In order to identify echistatin motifs required for selective recognition of ␣ v ␤ 3 and ␣ 5 ␤ 1 integrins, we expressed recombinant echistatin, eristostatin, and 15 hybrid molecules. We tested them for their ability to inhibit adhesion of different cell lines to fibronectin and von Willebrand factor and to express ligand-induced binding site epitope. The integrins are a family of cell surface glycoproteins that act as receptors for extracellular matrix (ECM) 1 proteins, or for membrane-bound counter-receptors on other cells. Each integrin is a heterodimer that contains an ␣ and a ␤ subunit, the pairing of which specifies the ligand binding abilities of integrins (1). Integrins can bind adhesive ligands and upon this binding undergo conformational changes leading to the exposure of neoepitopes recognized by specific monoclonal antibodies called anti-ligand-induced binding site (LIBS) antibodies (2).The Arg-Gly-Asp (RGD) sequence is the cell attachment site of a large number of adhesive ECM, blood, and cell surface proteins, and nearly half of the over 20 known integrins recognize this sequence in their adhesion protein ligands (3). In addition to the RGD motif, many adhesive receptors recognize other integrin-binding domains, such as the KQAGDV sequence (4) of fibrinogen ␥-chain, ILDV sequence of the CS1 region of fibronectin (5, 6), and RRETAWA sequence identified from a phage display library (7). It is known that the Arg and Asp residues are necessary but not sufficient to ensure binding activity. The RGD sequence is generally found to be associated with a series of probable ␤-bends, which result in a highly ordered structure. This highly ordered conformation might form the basis of the specific binding of many proteins containing this cell surface recognition sequence. Additional determinants of integrin specificity and the high affinity of RGDcontaining adhesive proteins for integrins may be the result of the specific conformation of the RGD sequence or by the amino acids immediately adjacent to the RGD site, creating an extended RGD locus.Disintegrins are snake venom proteins capable of binding to integrins and interfering with integrin function (8 -10). Disintegrins typically have an RGD sequence as their active site, except for barbourin containing a KGD sequence (11), and a new class of heterodimeric disintegrins such as EC3 and EMF10, containing MLD, VGD, and other recognition motifs (12). It appears that low molecular weight disintegrins, binding to integrins with an affinity approaching that of monoclonal antibodies, may represent a useful probe to identify functionally important motifs in the cell adhesion receptors. Scarborough et al. (13) postulated that the amino acid residue Cterminal to the RGD sequence determines selectivity of disintegrin for an integrin re...

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Section: Table I the Effect Of Recombinant Echistatin Eristostatin supporting

confidence: 91%

Structural Requirements of Echistatin for the Recognition of αvβ3 and α5β1Integrins

Wierzbicka-Patynowski¹,

Niewiarowski²,

Marcinkiewicz³

et al. 1999

Journal of Biological Chemistry

134

123

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“…The snake venom RGD-disintegrin salmosin induces apoptosis by disassembly of focal adhesions in bovine endothelial cells (30). Accutin, an RGD-disintegrin also induces apoptosis in endothelial cells (15). These results show significant differences between ALT-C and the RGD-disintegrins, regarding the effects on cell adhesion and proliferation.…”

Section: Figmentioning

confidence: 73%

“…These effects are opposite to those observed for most RGD-disintegrins, which inhibit angiogenesis and induce apoptosis (15,30). To our knowledge, this is the first report of a disintegrin acting as a survival factor.…”

mentioning

confidence: 92%

“…RGD-disintegrins bind mostly to ␣ 5 ␤ 1 or ␣ v ␤ 3 integrins in distinct cell types therefore inhibiting also cell adhesion to fibronectin (13). Accutin and triflavin, two RGD-disintegrins from Agkistrodon acutus and Trimeresurus flavoviridis venoms, respectively, inhibit angiogenesis and induce apoptosis in endothelial cells (15,16). The VAP1 protein (vascular apoptosis-inducing protein) isolated from Crotalus atrox venom is a metalloprotease/disintegrin that induces apoptosis (17).…”

mentioning

confidence: 99%

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Alternagin-C, a Disintegrin-like Protein, Induces Vascular Endothelial Cell Growth Factor (VEGF) Expression and Endothelial Cell Proliferation in Vitro

Cominetti

Terruggi

Ramos

et al. 2004

Journal of Biological Chemistry

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Alternagin-C (ALT-C), a disintegrin-like protein purified from the venom of the Brazilian snake Bothrops alternatus, interacts with the major collagen I receptor, the ␣ 2 ␤ 1 integrin, inhibiting collagen binding. Here we show that ALT-C also inhibits the adhesion of a mouse fibroblast cell line (NIH-3T3) to collagen I (IC 50 2.2 M). In addition, when immobilized on plate wells, ALT-C supports the adhesion of this cell line as well as of human vein endothelial cell (HUVEC). ALT-C (3 M) does not detach cells that were previously bound to collagen I. ALT-C (5 nM) induces HUVEC proliferation in vitro, and it inhibits the positive effect of vascular endothelial growth factor (VEGF) or FGF-2 on the proliferation of these cells, thus suggesting a common mechanism for these proteins. Gene expression analysis of human fibroblasts growing on ALT-C-or collagen-coated plates showed that ALT-C and collagen I induce a very similar pattern of gene expression. When compared with cells growing on plastic only, ALT-C up-regulates the expression of 45 genes including the VEGF gene and downregulates the expression of 30 genes. Fibroblast VEGF expression was confirmed by RT-PCR and ELISA assay. Up-regulation of the VEGF gene and other growth factors could explain the positive effect on HUVEC proliferation. ALT-C also strongly activates Akt/PKB phosphorylation, a signaling event involved in endothelial survival and angiogenesis. In conclusion, ALT-C acts as a survival factor, promoting adhesion and endothelial cell proliferation.Cell attachment to the extracellular matrix depends mostly on the integrins, a large family of glycoproteins expressed at the cell surface (1). Integrins are heterodimers formed of noncovalently associated ␣-and ␤-subunits (2). In many cells in culture, integrin-mediated adhesion results in specialized adhesion sites, named focal contacts (3). In these sites, structural and signaling proteins such as integrins, cytoskeletal proteins, and kinases are concentrated and initiate signal transduction pathways (4). Aggregation of integrin receptors, ligand occupancy, and tyrosine kinase-mediated phosphorylation are the key events that results in diverse processes such as cell migration and differentiation, tissue remodeling, cell proliferation, angiogenesis, and tumor cell invasion and metastasis (1, 5).Antagonists of integrins have been developed in order to provide powerful therapeutic approaches for the treatment of several types of cancer, such as antibodies to the ␣ v integrin (6). Synthetic peptides with the sequence Arg-Gly-Asp (RGD) can competitively block the binding of several integrins to their ligands and efficiently reduce platelet aggregation and the number of experimental metastasis (7). RGD peptides induce the disassembly of focal contacts in melanoma cells and disrupt the actin cytoskeleton (8). Disintegrins are small peptides derived from viperidae snake venoms with an internal RGD or KGD motif (9). Disintegrins can bind to integrins and interfere with integrin function. In platelets, disintegrins...

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“…Another family of proteins called disintegrins usually contain an RGD sequence, but in the case of one disintegrin (which is present in rotavirus), an LDV sequence is present (10). Disintegrins damage ECs or interfere with cell adherence (26)(27)(28). In the disintegrin, kistrin (from a snake venom) LDV can be substituted for RGD without compromising disintegrin function (29).…”

Section: Discussionmentioning

confidence: 99%

Evidence for a structural motif in toxins and interleukin-2 that may be responsible for binding to endothelial cells and initiating vascular leak syndrome

Baluna

Rizo

Gordon

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

181

124

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The dose-limiting toxicity of interleukin-2 (IL-2) and immunotoxin (IT) therapy in humans is vascular leak syndrome (VLS). VLS has a complex etiology involving damage to vascular endothelial cells (ECs), extravasation of f luids and proteins, interstitial edema, and organ failure. IL-2 and ITs prepared with the catalytic A chain of the plant toxin, ricin (RTA), and other toxins, damage human ECs in vitro and in vivo. Damage to ECs may initiate VLS; if this damage could be avoided without losing the efficacy of ITs or IL-2, larger doses could be administered. In this paper, we provide evidence that a three amino acid sequence motif, (x)D(y), in toxins and IL-2 damages ECs. Thus, when peptides from RTA or IL-2 containing this sequence motif are coupled to mouse IgG, they bind to and damage ECs both in vitro and, in the case of RTA, in vivo. In contrast, the same peptides with a deleted or mutated sequence do not. Furthermore, the peptide from RTA attached to mouse IgG can block the binding of intact RTA to ECs in vitro and vice versa. In addition, RTA, a fragment of Pseudomonas exotoxin A (PE38-lys), and fibronectin also block the binding of the mouse IgG-RTA peptide to ECs, suggesting that an (x)D(y) motif is exposed on all three molecules. Our results suggest that deletions or mutations in this sequence or the use of nondamaging blocking peptides may increase the therapeutic index of both IL-2, as well as ITs prepared with a variety of plant or bacterial toxins.

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C−H versus C−C Activation of Biphenylene in Its Reactions with Iron Group Carbonyl Clusters

Cited by 49 publications

References 41 publications

Structural Requirements of Echistatin for the Recognition of αvβ3 and α5β1Integrins

Structural Requirements of Echistatin for the Recognition of αvβ3 and α5β1Integrins

Alternagin-C, a Disintegrin-like Protein, Induces Vascular Endothelial Cell Growth Factor (VEGF) Expression and Endothelial Cell Proliferation in Vitro

Evidence for a structural motif in toxins and interleukin-2 that may be responsible for binding to endothelial cells and initiating vascular leak syndrome

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