Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
A bstract : The P ‐boranophosphates are efficient and near perfect mimics of natural nucleic acids in permitting reading and writing of genetic information with high yield and accuracy. Substitution of a borane (−BH 3 ) group for oxygen in the phosphate ester bond creates an isoelectronic and isosteric mimic of natural nucleotide phosphate esters found in mononucleotides, i.e., AMP and ATP, and in RNA and DNA polynucleotides. Compared to natural nucleic acids, the boranophosphate RNA and DNA analogs demonstrate increased lipophilicity and resistance to endo‐ and exonucleases, yet they retain negative charge and similar spatial geometry. Borane groups can readily be introduced into the NTP and dNTP nucleic acid monomer precursors to produce α‐ P ‐borano nucleoside triphosphate analogs (e.g., NTPαB and dNTPαB). The NTPαB and dNTPαB are, in fact, good to excellent substrates for RNA and DNA polymerases, respectively, and allow ready enzymatic synthesis of RNA and DNA with P ‐boranophosphate linkages. Further, boranophosphate polymer products are good templates for replication, transcription, and gene expression; boronated RNA products are also suitable for reverse transcription to cDNA. Fully substituted boranophosphate DNA can activate the RNase H cleavage of RNA in RNA:DNA hybrids. Moreover, certain dideoxy‐NTPαB analogs appear to be better substrates for viral reverse transcriptases than the regular ddNTPs, and may offer promising prodrug alternatives in antiviral therapy. These properties make boranophosphates promising candidates for diagnostics; aptamer selection; gene therapy; and antiviral, antisense, and RNAi therapeutics. The boranophosphates constitute a versatile family of phosphate mimics for processing genetic information and modulating gene function.
Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
A new method for synthesis of N-alkylated nucleosides was developed. Exceptionally mild and selective conversion of N-acyl to the corresponding N-alkyl nucleosides was achieved by reduction with borane-amine complexes. The borane-amine complexes were also used as efficient scavengers of a 4,4′-dimethoxytrityl (DMT) cation. Neutralization of the cation eliminated the boranophosphate group degradation during acidic DMT deprotection and allowed milder acidic conditions for the deprotection.
DNA binding compounds, such as benzo[e] (BePI) and benzo[g] pyridoindole (BgPI) derivatives, exhibit preferential stabilization of triple helices. We report here the synthesis of a series of pyrimidine triple-helix-forming oligo-2'-deoxyribonucleotides conjugated with these molecules. BePI was coupled to the 5-position of 2'-deoxyuridine via two linkers of different sizes attached to its 11-position and placed at either the 5'-end, inside the sequence, or at both the 5'-end and the internal positions using periodate oxidation of a diol-containing oligonucleotide followed by reductive coupling with amino-linked BePI. The same BePI derivatives were also linked to the oligonucleotide chain via internucleotidic phosphorothiolate or phosphoramidate linkages. A mixture of diastereoisomers was prepared as well as separate pure Rp and Sp isomers. A BePI derivative, with two different linkers attached to its 3-position, and BgPI derivatives were also linked to the 5-position of a 2'-deoxyuridine located at either the 5'-end or inside the sequence, as well as to the β- anomeric position of an additional 2'- deoxyribose placed inside the sequence. The binding properties of these oligonucleotide−benzopyridoindoles conjugates with their double-stranded DNA target was studied by absorption spectroscopy.
al., 2009). Low complexity, no known post-processing modifications, simple detection and amplification methods, tissue-specific expression profiles, and sequence conservation between humans and model organisms make extracellular miRNAs ideal candidates for genomic biomarkers to reflect and study various physiopathological conditions of the body.Ideally, the most clinically powerful information would come directly from the tissue of interest.To understand cancer, one must look at malignant cells, much as one must analyze brain tissue to understand the complexities of neuroscience.However, many of these tissues are difficult to access or impossible to reach without potential injury to the patient.Alternative, or "surrogate", tissues can provide a means of assessing the genomic changes in the tissue of interest, without fear of harming the donor.For example, surrogate tissues may contact the tissue of interest and retain sloughed cells, secreted molecules or the contents of dying cells.While these molecular signals may not exactly mirror the tissue of origin, in many cases they are reproducible and can clearly point to underlying biology.Clinical material suitable for biomarker testing can be divided into 2 different types.The first are those that require minimally invasive procedures to obtain.This type includes blood, cerebrospinal fluid, tissue biopsies and so on.Type 2 tissues are those that can be obtained without any invasive means: hair, saliva, tears, epidermal cells, urine, etc.In some cases, acquisition of the material may not be passive.Examples of Type 1 and Type 2 samples are listed in Table 1.
