Calcium-dependent oligonucleotide antagonists specific for L-selectin.

O'Connell, Dan; Koenig, Andrea; Jennings, Susan D.; Hicke, Brian J.; Han, Huiling; Fitzwater, Tim; Chang, Ying-Fon; Varki, Nissi; Parma, David H.; Varki, Ajit

doi:10.1073/pnas.93.12.5883

Cited by 98 publications

(74 citation statements)

References 37 publications

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“…In order to increase the specificity of selected RNA aptamers, we have utilized a combinatorial library approach by pretreating RNA aptamers with GST-Sepharose 4B before each round of SELEX selection, from the third round to the eighth and final round. Although this combinatorial library approach has been successfully used to isolate aptamers blocking ligand-receptor interactions between eukaryotic cells and viruses (2,5,8) or between eukaryotic cells themselves (17,22,29), the technique has not been applied to the selection of ligands blocking an interaction between bacterial and eukaryotic cells. Our studies indicate that the SELEX approach is a useful tool to study the roles of bacterial proteins in pathogenesis and invasion of host cells, as well as to provide insights into the mechanisms of pathogen-host cell interactions.…”

Section: Discussionmentioning

confidence: 99%

“…Bacterial self-association is an important virulence trait in enterotoxigenic strains of Escherichia coli and in Vibrio cholerae (1). These data indicated that the structural protein PilS of the type IVB pili might play important roles in the pathogenesis of S. enterica serovar Typhi in humans.The SELEX (systematic evolution of ligands by exponential enrichment) method (28) is an oligonucleotide-based combinatorial library selection procedure that has been used extensively to isolate ligands (aptamers) that bind to proteins (3,6,9,22,32), cell surface epitopes (19,21), and other targets (4,12,13,17). Although in recent years SELEX has become increasingly important in the study of functions of proteins, as well as in the fields of drug discovery and identification of antagonists against many functional proteins, this in vitro selection strategy to generate inhibitors of the functions of bacterial proteins remains underutilized.…”

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confidence: 99%

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Aptamers That Preferentially Bind Type IVB Pili and Inhibit Human Monocytic-Cell Invasion by Salmonella enterica Serovar Typhi

Pan¹,

Zhang

Wu³

et al. 2005

Antimicrob Agents Chemother

109

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Salmonella enterica serovar Typhi is an important pathogen exclusively for humans and causes typhoid or enteric fever. It has been shown that type IVB pili, encoded by the S. enterica serovar Typhi pil operon located in Salmonella pathogenicity island 7, are important in the pathogenic process. In this study, by using both an adhesion-invasion assay and fluorescence quantitative PCR analysis, we demonstrated that the entry of type IVB piliated S. enterica serovar Typhi A21-6 (pil ؉ Km r ) into human THP-1 monocytic cells was greater than that of a nonpiliated S. enterica serovar Typhi pilS::Km r (pil mutant) strain. We have applied a systematic evolution of ligands by exponential enrichment approach to select oligonucleotides (aptamers) as ligands that specifically bind to type IVB pili. Using this approach, we identified a high-affinity single-stranded RNA aptamer (S-PS 8.4 ) as a type IVB pilus-specific ligand and further found that the selected aptamer (S-PS 8.4 ) could significantly inhibit the entry of the piliated strain (but not that of the nonpiliated strain) into human THP-1 cells. The binding affinities between aptamers and pre-PilS (structural protein of type IVB pili) were determined by nitrocellulose filter-binding assays, and the K d value was determined to be 8.56 nM for the S-PS 8.4 aptamer alone. As an example of an aptamer against type IVB pili of S. enterica serovar Typhi, the aptamer S-PS 8.4 can serve as a tool for analysis of bacterial type IVB pilus-host cell interactions and may yield information for the development of putative new drugs against S. enterica serovar Typhi bacterial infections, useful both in prevention of infection and in therapeutic treatment.Of the more than 2,300 closely related Salmonella serovars identified, Salmonella enterica serovar Typhi is an important pathogen exclusively for humans and can be transmitted through contaminated food and water. It causes typhoid or enteric fever, which is a serious public health problem in developing countries. The genome of S. enterica serovar Typhi contains three large inserts (pathogenicity islands) (11), relative to the chromosome of Salmonella enterica serovar Typhimurium, which is normally noninvasive for humans. The type IVB pil operon of S. enterica serovar Typhi is located in Salmonella pathogenicity island 7 (18) and contains a pilS gene encoding the structural pilin (36, 37). It has been demonstrated that a pilS mutant of S. enterica serovar Typhi exhibited muchreduced adhesion to and invasion of human epithelial gastrointestinal cells in vitro and that purified soluble pre-PilS protein, retaining the signal sequence normally cleaved when the protein is excreted to form insoluble pili based on polymerized PilS, inhibited bacterial invasion (37). The structure of the N-terminally truncated type IVB structural pilin from S. enterica serovar Typhi was determined by nuclear magnetic resonance analysis (34). Type IVB pili, composed largely of polymerized PilS protein, also mediate bacterial self-association, but only when the...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Aptamers That Preferentially Bind Type IVB Pili and Inhibit Human Monocytic-Cell Invasion by Salmonella enterica Serovar Typhi

Pan¹,

Zhang

Wu³

et al. 2005

Antimicrob Agents Chemother

109

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“…that published for E-selectin (Scheffler et al, 1995), will be conducive for this approach. Reduction of cross-reactions between selectins can be sought to be attained by systematic evolution of ligands with the exponential enrichment technology, as shown for isolation of oligonucleotide ligands for L-selectin surpassing the binding affinity of common oligosaccharides by a factor of IO4-1O5 (O'Connell et al, 1996). RNA molecules can thus apparently form surfaces that mimic those of oligosaccharides and also those of proteins, as has already been documented (Keene, 1996).…”

Section: C-type Lectinsmentioning

confidence: 99%

Animal Lectins

Gabius

1997

European Journal of Biochemistry

435

342

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Protein and lipid glycosylation is no longer considered as a topic whose appeal is restricted to a limited number of analytical experts perseveringly pursuing the comprehensive cataloguing of structural variants. It is in fact arousing curiosity in various areas of basic and applied bioscience. Well founded by the conspicuous coding potential of the sugar part of cellular glycoconjugates which surpasses the storage capacity of oligonucleotide-or oligopeptide-based code systems, recognition of distinct oligosaccharide ligands by endogenous receptors, i.e. lectins and sugar-binding enzymes or antibodies, is increasingly being discovered to play salient roles in animal physiology. Having inevitably started with a descriptive stage, research on animal lectins has now undubitably reached maturity. Besides listing the current categories for lectin classification and providing presentations of the individual families and their presently delineated physiological significance, this review places special emphasis on tracing common structural and functional themes which appear to reverberate in nominally separated lectin and animal categories as well as lines of research which may come to fruition for medical sciences.Keywords: lectin ; glycoprotein; glycolipid; cell adhesion ; molecular recognition ; inflammation; infection ; fertilization ; signal transduction ; tumor biology.The putative multiplicity of functional implications for protein and lipid glycosylation has fueled vigorous and prolific research activities in the last decade. Although glycobiologists continue to be afflicted with the problem of precisely defining the physiological significance of the puzzling variability and complex pattern of carrier-attached saccharide chains, the notion of inherent ligand properties for recognitive protein-carbohydrate interactions is already well established

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“…The aptamers were tested for selectivity using only protein targets: full-length BACE1 coupled to agarose and an antibody-derivatized agarose. Other selections of RNA aptamers against soluble extracellular fragments of membrane proteins, albeit without any testing for selectivity, were reported for: L-selectin (a cell adhesion molecule) [24], β-catenin (a component of the Wnt signaling pathway) [25] and KRAS protein (a molecular switch in the propagation of receptor signals related to cell proliferation, division and mortality) [26]. There were two reports on selections of DNA aptamers against soluble extracellular fragments of the following membrane proteins: hemagglutinin (located in the influenza virus envelope) [27] and MUC1 (located in the membrane of epithelial cells and overexpressed on some cancer cells) [28].…”

Section: Aptamers Selected Using Soluble Fragments Of Membrane Proteinsmentioning

confidence: 99%

The selection of aptamers specific for membrane molecular targets

Janas

2011

Cellular and Molecular Biology Letters

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Abbreviations used: AChR -acetylcholine receptor; CHO cells -Chinese hamster ovary cells; CT -cytoplasmic tail; DOPC -dioleoylphosphatidylcholine; DOPSdioleoylphosphatidylserine; ECD -extracellular domain; GPCR -G-protein-coupled receptor; HER3 -human epidermal growth factor receptor-3; IgM -immunoglobulin M; mAbs -monoclonal protein antibodies; MBP -maltose binding protein; NT -neurotensin; PSMA -prostate-specific membrane antigen; SELEX -systematic evolution of ligands by exponential enrichment Abstract: A growing number of RNA aptamers have been selected experimentally using the SELEX combinatorial approach, and these aptamers have several advantages over monoclonal protein antibodies or peptides with respect to their applications in medicine and nanobiotechnology. Relatively few successful selections have been reported for membrane molecular targets, in contrast to the situation with non-membrane molecular targets. This review compares the procedures and techniques used in selections against membrane proteins and membrane lipids. In the case of membrane proteins, the selections were performed against soluble protein fragments, detergent-membrane protein mixed micelles, whole cells, vesicles derived from cellular membranes, and enveloped viruses. Liposomes were used as an experimental system for the selection of aptamers against membrane lipids. RNA structure-dependent aptamer binding for rafts in lipid vesicles was reported. Based on the selected aptamers against DOPC and the amino acid tryptophan, a specific passive membrane transporter composed of RNA was constructed. The determination of the selectivity of aptamers appears to be a crucial step in a selection, but has rarely been fully investigated. The selections, which use whole cells or vesicles derived from membranes, can yield aptamers not only against proteins but also against membrane lipids.

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Calcium-dependent oligonucleotide antagonists specific for L-selectin.

Cited by 98 publications

References 37 publications

Aptamers That Preferentially Bind Type IVB Pili and Inhibit Human Monocytic-Cell Invasion by Salmonella enterica Serovar Typhi

Aptamers That Preferentially Bind Type IVB Pili and Inhibit Human Monocytic-Cell Invasion by Salmonella enterica Serovar Typhi

Animal Lectins

The selection of aptamers specific for membrane molecular targets

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