Ribonucleosides and Rna

Eaton, Bruce E.; Pieken, Wolfgang A.

doi:10.1146/annurev.bi.64.070195.004201

Cited by 97 publications

(40 citation statements)

References 41 publications

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“…To be applicable in cell culture studies, we generated nucleaseresistant aptamers by screening oligonucleotide libraries in which all pyrimidine residues were substituted by 2Ј-amino-2Ј-deoxy-modified monomers (34 -38). This modification is known to protect against the majority of serum nucleases so that such aptamers can be applied in the presence of biological materials in which normal RNA would rapidly degrade (39,40).…”

Section: Resultsmentioning

confidence: 99%

A Y2 Receptor Mimetic Aptamer Directed against Neuropeptide Y

Proske

Höfliger

Söll

et al. 2002

Journal of Biological Chemistry

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Neuropeptide Y (NPY) is a 36-amino acid neuropeptide that exerts its activity by at least five different receptor subtypes that belong to the family of G-proteincoupled receptors. We isolated an aptamer directed against NPY from a nuclease-resistant RNA library. Mapping experiments with N-terminally, C-terminally, and centrally truncated analogues of NPY revealed that the aptamer recognizes the C terminus of NPY. Neuropeptide Y (NPY)1 is a 36-amino acid neuropeptide and is one of the most conserved peptides during evolution (1, 2). It shows high homology to the other members of the pancreatic polypeptide hormone family, namely pancreatic polypeptide and peptide YY (3, 4). NPY is widely distributed in the central and peripheral nervous system (5). It modulates a variety of physiological processes such as the central regulation of food intake (6, 7), vasoconstriction, memory retention (8, 9), and regulation of circadian rhythm (10 -12). NPY transmits its activity by at least three receptor subtypes (Y 1 , Y 2 , and Y 5 ), which all belong to the large family of G-protein-coupled receptors (GPCR). They are coupled to G i proteins and accordingly inhibit adenylate cyclase (13, 14). The different receptor subtypes are distributed heterogeneously in various tissues in the central nervous system and the periphery and so far it is not understood how NPY selectively activates a particular receptor pathway.In general, structural insight how GPCRs are activated is scarce. Only recently the first crystal structure of a Gprotein-coupled receptor, rhodopsin, has been solved and provided insight into the molecular mechanism of GPCR activation (15). However, these structural analyses are highly advanced and cannot be considered routine. Furthermore, because the ligand is covalently bound in rhodopsin, the process of ligand approaching is still unknown. Accordingly, biochemical methods that facilitate our understanding of GPCRs are urgently required. All current information on structure/activity or structure/affinity relationships of NPY and its G-protein-coupled receptor subtypes have been obtained by indirect methods such as site-directed mutagenesis in transmembrane regions and extracellular loops of the receptors (16) and replacement of amino acid residues in NPY (17-19). Modified analogues and recombinant receptors are excellent tools to study ligand-receptor interaction in vitro or in cell lines. However, they cannot be applied to characterize interactions in vivo because the in vivo expression of each modification would require an individual transgenic animal. To circumvent these problems, selective low molecular weight antagonists have been developed (20,21). These small organic molecules, however, do not necessarily bind to the receptor in a way similar to the endogenous ligand. For example, only partial overlapping of the binding site has been shown for BIBP3226, and in the substance P and angiotensin systems completely different binding sites for agonist and antagonist were identified (22). Mapping of the Y 1 recepto...

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Section: Resultsmentioning

confidence: 99%

A Y2 Receptor Mimetic Aptamer Directed against Neuropeptide Y

Proske

Höfliger

Söll

et al. 2002

Journal of Biological Chemistry

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“…The (2'R)-isomer could be used to increase nuclease stability of DNA. It could be introduced into an oligonucleotide chain either by chemical synthesis or enzymatically, since 5'-triphosphates of 2'-(alkoxyamino)-2'-deoxynucleosides are substrates for DNA polymerases [28].…”

Section: Results Andmentioning

confidence: 99%

Synthesis of (2′S)‐ and (2′R)‐2′‐Deoxy‐2′‐[(2‐methoxyethoxy)amino] Pyrimidine Nucleosides and Oligonucleotides

Zatsepin¹,

Ivanova²,

Oretskaya

2004

Chemistry & Biodiversity

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Syntheses of specified 2'-modified nucleosides were achieved: a) via oximation of the 5',3'-blocked 2'-oxocytidine, followed by reduction, or b) by intramolecular nucleophilic addition of 3'-(2-methoxyethoxy)carbamate to the 2'-position with opening of O(2),2'-anhydrouridine. For the first time, 3'-phosphoroamidites of these 2'-modified nucleosides were successfully incorporated into oligonucleotides by solid-phase synthesis. Incorporation of 2'-modified nucleotides into oligodeoxyribonucleotides had a negative effect on the duplex T(m) values with the DNA or RNA complements. Nevertheless, modified nucleotides have shown good target recognition; the (S)-isomer binds preferably to RNA and the (R)-isomer to DNA. Both modified nucleosides significantly increased nuclease resistance of the oligodeoxyribonucleotides.

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“…Furthermore, 2 0 -modifications is known to increase the stability against chemical and enzymatic degradation. [122][123][124][125] Very recently, Lauridsen et al reported a review article describing the enzymatic recognition capabilities of various 2 0 -modified nucleotides. 126 Stemming from their initial enzymatic recognition studies, 2 0 -amino pyrimidines, 2 0 -fluoro pyrimidines and 2 0 -O-Methyl nucleotides have been successfully applied in aptamer development by conventional SELEX-based methodologies.…”

Section: Chemically Modified Aptamer-oligonucleotide Chimeramentioning

confidence: 99%