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21.
Boys ML Schretzman LA Chandrakumar NS Tollefson MB Mohler SB Downs VL Penning TD Russell MA Wendt JA Chen BB Stenmark HG Wu H Spangler DP Clare M Desai BN Khanna IK Nguyen MN Duffin T Engleman VW Finn MB Freeman SK Hanneke ML Keene JL Klover JA Nickols GA Nickols MA Steininger CN Westlin M Westlin W Yu YX Wang Y Dalton CR Norring SA 《Bioorganic & medicinal chemistry letters》2006,16(4):839-844
We describe a series of 1,2,4-oxadiazoles, which are potent antagonists of the integrin alpha(v)beta3 and, in addition, show selectivity relative to the other beta3 integrin alpha(IIb)beta3. In whole cells, the majority of these analogs also demonstrated modest selectivity against other alpha(v) integrins such as alpha(v)beta1 and alpha(v)beta6. 相似文献
22.
Caswell CC Barczyk M Keene DR Lukomska E Gullberg DE Lukomski S 《The Journal of biological chemistry》2008,283(52):36168-36175
Many pathogenic bacteria interact with human integrins to enter host cells and to augment host colonization. Group A Streptococcus (GAS) employs molecular mimicry by direct interactions between the cell surface streptococcal collagen-like protein-1 (Scl1) and the human collagen receptor, integrin alpha2beta1. The collagen-like (CL) region of the Scl1 protein mediates integrin-binding, although, the integrin binding motif was not defined. Here, we used molecular cloning and site-directed mutagenesis to identify the GLPGER sequence as the alpha2beta1 and the alpha11beta1 binding motif. Electron microscopy experiments mapped binding sites of the recombinant alpha2-integrin-inserted domain to the GLPGER motif of the recombinant Scl (rScl) protein. rScl proteins and a synthetic peptide harboring the GLPGER motif mediated the attachment of C2C12-alpha2+myoblasts expressing the alpha2beta1 integrin as the sole collagen receptor. The C2C12-alpha11+myoblasts expressing the alpha11beta1 integrin also attached to GLPGER-harboring rScl proteins. Furthermore, the C2C12-alpha11+cells attached to rScl1 more efficiently than C2C12-alpha2+cells, suggesting that the alpha11beta1 integrin may have a higher binding affinity for the GLPGER sequence. Human endothelial cells and dermal fibroblasts adhered to rScl proteins, indicating that multiple cell types may recognize and bind the Scl proteins via their collagen receptors. This work is a stepping stone toward defining the utilization of collagen receptors by microbial collagen-like proteins that are expressed by pathogenic bacteria. 相似文献
23.
Two type XII-like collagens localize to the surface of banded collagen fibrils 总被引:2,自引:6,他引:2 下载免费PDF全文
D R Keene G P Lunstrum N P Morris D W Stoddard R E Burgeson 《The Journal of cell biology》1991,113(4):971-978
Two recently identified collagen molecules, termed twelve-like A and twelve-like B (TL-A and TL-B) have properties similar to type XII collagen. These molecules have been localized in human and calf tissues by immunoelectron microscopy. The observations strongly suggest that both molecules are located along the surface of banded collagen fibers. The epitopes recognized by the antibodies are contained in large, nontriple-helical domains at one end of the collagen helix. The epitopes are visualized at a distance from the surface of the banded fibers roughly equal to the length of the nonhelical domains, suggesting that the nonhelical domains extend from the fibril, while the triple-helical domains are likely to bind directly to the fibril surface. Occasionally, both TL-A and TL-B demonstrate periodic distribution along the fibril surface. The period corresponds to the primary interband distance of the banded fibrils. Not all fibrils in a fiber bundle are labeled, nor is the labeling continuous along the length of labeled fibrils. Simultaneous labeling of TL-A and type VI collagen only rarely shows colocalization, suggesting that TL-A and TL-B do not mediate interactions between the type VI collagen beaded filaments and banded collagen fibrils. Also, interfibrillar distances are approximately equivalent in the presence and absence of these type XII-like molecules. While the results do not directly indicate a specific function for these molecules, the localization at the fibril surface suggests that they mediate interactions between the fibrils and other matrix macromolecules or with cells. 相似文献
24.
Large complex globular domains of type VII procollagen contribute to the structure of anchoring fibrils 总被引:18,自引:0,他引:18
G P Lunstrum L Y Sakai D R Keene N P Morris R E Burgeson 《The Journal of biological chemistry》1986,261(19):9042-9048
Type VII collagen, in the form of an antiparallel dimer, is a major protein component of anchoring fibrils. The ultrastructural appearance of these fibrils suggests that they may serve to anchor the basement membrane zone to the underlying connective tissue matrix. We report here the identification and initial characterization of Type VII procollagen, recovered from the media of epidermoid carcinoma cell cultures. Immunoblotting using monospecific antibodies to Type VII procollagen identifies a single, homogeneous band of at least Mr 320,000 following disulfide bond reduction. This chain contains 170 kDa of collagen triple helix and 150 kDa of non-helical domain at the carboxyl terminus. Pepsin digestion of this material yields Type VII collagen identical to that isolated from whole tissue and a series of quasi-stable peptides derived from the carboxyl-terminal region. Cell extracts contain procollagen chains identical in size to those secreted into the media. There is no evidence for processing of this material in cell culture. Partial purification by velocity sedimentation and transmission electron microscopic observation following rotary shadowing reveals both monomers (426 nm) and dimers (785 nm). Dimers are antiparallel and interact through 60-nm overlap, with amino-terminal globular domains present at the ends of the overlap. The multi-domain carboxyl-terminal region appears as three similar arms originating from a centralized globular region adjacent to the collagen helix. The carboxyl globular domain is present in whole tissue and may participate in the unique fibril form of this collagen. The amino-terminal globule may function in the antiparallel assembly of dimers. 相似文献
25.
Reiter LA Freeman-Cook KD Jones CS Martinelli GJ Antipas AS Berliner MA Datta K Downs JT Eskra JD Forman MD Greer EM Guzman R Hardink JR Janat F Keene NF Laird ER Liras JL Lopresti-Morrow LL Mitchell PG Pandit J Robertson D Sperger D Vaughn-Bowser ML Waller DM Yocum SA 《Bioorganic & medicinal chemistry letters》2006,16(22):5822-5826
Using SAR from two related series of pyrimidinetrione-based inhibitors, compounds with potent MMP-13 inhibition and >100-fold selectivity against other MMPs have been identified. Despite high molecular weights, clogPs, and polar surface areas, the compounds are generally well absorbed and have excellent pharmacokinetic (PK) properties when dosed as sodium salts. In a rat fibrosis model, a compound from the series displayed no fibrosis at exposures many fold greater than its MMP-13 IC50. 相似文献
26.
EO Ogueji CD Nwani SC Iheanacho CE Mbah CO Okeke A Yaji 《African Journal of Aquatic Science》2018,43(3):293-303
Indiscriminate discharge of pharmaceutical waste into the aquatic ecosystem may pose serious health challenges to aquatic biota. The effect of acute exposure to ibuprofen was evaluated using changes in behaviour and haematological parameters under static bio-assay method in Clarias gariepinus. Test specimens were exposed to acute concentrations of ibuprofen (0.28, 0.33, 0.38, 0.43 and 0.48 mg l?1) for 24, 48, 72 and 96 h durations respectively. Behavioural and phenotypic changes were observed in surviving fish. There were significant (p < 0.05) concentration and duration-dependent increases in erythrocyte (RBC), haemoglobin (Hb), pack cell volume (PCV) and leukocytes (WBC) in treated fish compared to the control. Insignificant decreases (p > 0.05) in mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH) and mean corpuscular haemoglobin concentration (MCHC) were observed in treated fish compared to the control. Ibuprofen elicited dose and duration- dependent decrease in neutrophil counts with the decreases being significant (p < 0.05) in the higher doses of 0.43 and 0.48 mg l?1. Ibuprofen did not elicit any significant changes in monocytes, basophils and eosinophils. Changes observed in this study showed that ibuprofen negatively affected the health of the fish and we recommend that discharge of ibuprofen into the aquatic environment should be monitored and controlled. 相似文献
27.
RNA regulons: coordination of post-transcriptional events 总被引:10,自引:0,他引:10
Keene JD 《Nature reviews. Genetics》2007,8(7):533-543
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29.
Anionic PAMAM dendrimers as drug delivery vehicles for transition metal-based anticancer drugs 总被引:1,自引:0,他引:1
Michelle J. Pisani Nial J. Wheate F. Richard Keene J. Grant Collins 《Journal of inorganic biochemistry》2009,103(3):373-380
The use of anionic half-generation poly(amidoamine) dendrimers as drug delivery vehicles for [Pt(S,S-dach)(5,6-Me2phen)]2+ (56MESS) (where S,S-dach = 1S,2S-diaminocyclohexane; 5,6-Me2phen = 5,6-dimethyl-1,10-phenanthroline) and [{Δ,Δ-Ru(phen)2}2(μ-bb7)]4+ (Rubb7) (where phen = 1,10-phenanthroline; bb7 = 1,7-bis[4-(4′-methyl-2,2′-bipyridyl)heptane]) has been studied by nuclear magnetic resonance spectroscopy. From one- and two-dimensional 1H NMR spectra both 56MESS and Rubb7 were found to bind to the surface of generation 3.5, 4.5, 5.5 and 6.5 dendrimers through electrostatic interactions. The higher charge and larger size of Rubb7 resulted in stronger binding to all dendrimer generations (Kb ? 2 × 105 M−1) compared with 56MESS (Kb ? 1 × 104 M−1). Interestingly, there appeared to be no observable trend between dendrimer size and binding constant strength. The size of the free and 56MESS-bound dendrimers were examined using pulsed-gradient spin-echo NMR. The dendrimers ranged in hydrodynamic diameter from 11 to 20 nm and in all cases were larger than their corresponding full-generation dendrimer. Upon the addition of 56MESS the diameter of the dendrimers increased, consistent with surface binding. 相似文献
30.