A Multi-Model Approach to Nucleic Acid-Based Drug Development

Gautherot, Isabelle; Sodoyer, Régis

doi:10.2165/00063030-200418010-00004

Cited by 8 publications

(4 citation statements)

References 200 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The past decade has seen an upsurge of interest in nucleic acid-based drug development. 254 This is mainly due to the realization that modified oligomers (oligos), with improved properties, can be used in the sequence specific control of gene expression and have immense potential as therapeutic agents. 236,[255][256][257][258][259] A principle mode of action of these modified oligos is through binding to a specific mRNA sequence associated with a disease and thereby (a) terminating the translation of a defective protein (antisense) 236,255,257 or (b) altering splice sites.…”

Section: Oligonucleoside Boranophosphatesmentioning

confidence: 99%

Nucleoside and Oligonucleoside Boranophosphates: Chemistry and Properties

et al. 2007

View full text Add to dashboard Cite

4757 3.4. Separation and Spectral Properties of Diastereomers of Borane-Containing Cyclic Monophosphates 4758 4. Nucleoside Boranodiphosphates 4758 4.1. Synthesis of Nucleoside 5′-(R-P-Borano)diphosphates 4.1.1. Synthesis via a Boranophosphoramidate Approach 4.1.2. Synthesis via an Oxathiaphospholane Approach 4.1.3. Synthesis via a Phosphite Approach 4.2. Separation and Configuration Determination of the Diastereomers of NDPRB 4.2.1. Separation of the Diastereomers of NDPRB 4.2.2. Configuration Determination of the Diastereomers of NDPRB 4.3. Substrate Properties of NDPRB Analogues with NDPK, Pyruvate Kinase, and Creatine Kinase 4.3.1. Substrate Properties of NDPRB Analogues with NDPK 4.3.2. Binding Affinity of NDPRB Analogues with Pyruvate Kinase (PK) and Creatine Kinase (CK) 4.4. Synthesis of Nucleoside 5′-(β-P-Borano)diphosphates 5. Nucleoside Boranotriphosphates 5.1. Synthesis of Nucleoside 5′-(R-P-Borano)triphosphates 5.1.1. Synthesis via a Phosphoramidite Approach 5.1.2. Synthesis via a Phosphite Approach 5.2. Separation and Configuration Determination of the Diastereomers of NTPRB 5.2.1. Separation of the Diastereomers of NTPRB 5.2.2. Configuration Determination of the Diastereomers of NTPRB 5.3. Substrate Properties of NTPRB Analogues with Viral RTs and PK 5.3.1. Substrate Properties of dNTPRB Analogues with Viral RTs and DNA Polymerases 5.3.2. Substrate Properties of ddNTPRB Analogues with Viral RTs and DNA Polymerases 5.3.3. Binding Affinity of NTPRB Analogues with Rabbit Muscle PK 5.4. Synthesis of Borane-Containing Novel Triphosphate Analogues 5.4.1. Synthesis of β-P-BH 3 -and γ-P-BH 3 -Modified Triphosphates and Diboranotriphosphates

show abstract

Section: Oligonucleoside Boranophosphatesmentioning

confidence: 99%

Nucleoside and Oligonucleoside Boranophosphates: Chemistry and Properties

et al. 2007

View full text Add to dashboard Cite

show abstract

“…For details the interested reader is referred to the reviews by Sohail & Southern 4 and Gautherot & Sodoyer. 5 To identify accessible target sites on a complex and highly structured RNA by any of these methods is a time and labour consuming process that does not always meet with success. In general, only one out of eight antisense oligonucleotides is thought to be efficient for knockdown of target genes.…”

Section: Introductionmentioning

confidence: 99%

Gaining Target Access for Deoxyribozymes

Schubert

Fürste

Werk

et al. 2004

Journal of Molecular Biology

View full text Add to dashboard Cite

“…Detection of single nucleotide polymorphisms and point mutations is difficult and sometimes impossible if the underlying sequence is inaccessible to hybridization. Since RNA folding programs based on nearest-neighbor thermodynamic parameters are not totally reliable for long transcripts ( − ), sequences that are available for hybridization must be determined experimentally for each RNA. Several strategies have been described that lessen the interference due to secondary structures.…”

mentioning

confidence: 99%

Modified Bases in RNA Reduce Secondary Structure and Enhance Hybridization

et al. 2004

View full text Add to dashboard Cite

Secondary structure in RNA targets is a significant barrier to short DNA probes. However, when such targets are the end product of an in vitro amplification scheme, it is possible to carry out transcription in the presence of nucleoside triphosphate analogues that reduce secondary structure of the RNA without impairing subsequent hybridization. Here we show that nucleoside triphosphates of 2-aminoadenine (nA) and 2-thiouracil (sU) are taken up by T7 RNA polymerase and that the resulting RNA possesses reduced secondary structure and improved accessibility to DNA probes. The hybridization properties of short RNA transcripts were studied using a new gel mobility shift assay from which melting temperatures were determined. RNA hairpins that contained nA and sU were able to hybridize to DNA probes under conditions where the unmodified hairpins did not. DNA-RNA hybrids that contained nA and sU in the RNA strand exhibited enhanced specificity, increased stability, and greater equality of base pairing strength than the same hybrids without modifications. Substitution of guanine (G) with inosine (I) further reduced secondary structure, but RNA with this base hybridized nonselectively. The high stability of nA-T and A-sU base pairs in DNA-RNA hybrids, combined with the destabilizing effect of the nA-sU couple in RNA targets, accounts for the improved hybridization properties. These results suggest that incorporation of nA and sU during in vitro transcription is a promising strategy for enhancing the performance of oligomeric DNA probes with an RNA target.

show abstract

A Multi-Model Approach to Nucleic Acid-Based Drug Development

Cited by 8 publications

References 200 publications

Nucleoside and Oligonucleoside Boranophosphates: Chemistry and Properties

Nucleoside and Oligonucleoside Boranophosphates: Chemistry and Properties

Gaining Target Access for Deoxyribozymes

Modified Bases in RNA Reduce Secondary Structure and Enhance Hybridization

Contact Info

Product

Resources

About