Chemically Modified Oligonucleotides as Probes and Inhibitors

Abstract

Oligonucleotides bind specifically to single‐stranded nucleic acids to form a double helix if there is a complementary antiparallel nucleotide sequence. In addition, certain oligonucleotides bind specifically to a variety of proteins. Therefore, biological processes involving these nucleic acids or proteins can be modulated (normally inhibited) by addition of the respective oligonucleotides. The effects of these oligonucleotides and the fields of potential application can be broadened by the introduction of chemically modified nucleotides. For instance, replacing oligonucleotide phosphate groups by methylphosphonates results in the loss of one negative charge per nucleotide and the oligonucleotide becomes more lipophilic. An oligonucleotide carrying a reactive group can modify its binding partner. An oligonucleotide covalently linked to a dye can be localized in a biological specimen. Oligonucleotides attached to an enzyme can be detected in very small amounts since the enzyme can catalyze the formation of large amounts of the substance assayed (e.g., a fluorescent product). An important biochemical application is the detection and localization of a messenger RNA or its gene. Medical applications include the detection of bacterial or viral sequences. There is also great interest in inhibiting the translation of messenger RNA and the transcription and replication of DNA. So‐called antisense oligonucleotides are currently being used for the inhibition of protein biosynthesis and of reverse transcription of retroviruses.

Stereoselective N-Glycosylation of 2-Deoxythioribosides for Fluorescent Nucleoside Synthesis

“…The mixture was extracted with CHCl 3 (3 × 400 mL), dried, filtered, and evaporated in vacuo. The crude material was subjected to column chromatography on silica gel (CH 2 Cl 2 /MeOH, 95:5) to give an inseparable isomer mixture of thioglycoside 3 (α/β = 1.0:1. p-Tolyl-3-O-acetyl-1-thio-5-O-triisopropylsilyl-2-deoxy-α,β-D-ribofuranoside (5). To a stirring solution of thioglycosides 4α and 4β (α/β = 1.0:1.8, 2.05 g, 5.17 mmol) in MeCN (35 mL) were added Et 3 N (0.86 mL, 6.20 mmol), Ac 2 O (0.58 mL, 6.20 mmol), and DMAP (0.063 g, 0.52 mmol).…”

Fc–ssDNA conjugate: electrochemical properties in a borate buffer and adsorption on gold electrode surfaces

“…The adsorption of bioorganic molecules such as peptides and oligonucleotides on electrode surfaces has attracted the attention of many scientists in the last decade because of its widespread application in medical devices [1,2] and biosensors [3][4][5]. By incorporating an electroactive motif into oligonucleotides, the electrochemical detection and subsequent understanding of the properties of a single stranded, hybridized and mismatched DNA is possible [6][7][8][9][10][11][12][13][14].…”

The SP Diastereomer of a Dinucleoside Methylphosphonate Methanol Solvate Containing Thymine and N3-Methyl-4-thiothymine Bases

“…The biological activity of chiral oligonucleotide analogues (e.g. methylphosphonates) and their potential applications in the antisense strategy for the artificial control of gene expression has stimulated wide interest in this class of compounds (Englisch & Gauss, 1991;Miller, 1989). In contrast, only three solid-state structures of dinucleoside methylphosphonates are known to date, namely SpdAp(Me)T (Chacko, Lindner, Saenger & Miller, 1983), Rp-dCp(Me)G (Han et al, 1990) and SpTp(Me)sT (where sT is 4-thiothymidine) (Szab6, Norrus, Norrestam & Stawifiski, 1993).…”