Brian C. Froehler

Synthesis of DNA via deoxynucleoside H-phosphonate intermediates.

Deoxynucleoside H-phosphonates are used in the chemical synthesis of deoxyoligonucleotides up to 107 bases in length. The biological activity of the synthetic DNA is assessed by cloning into M13 and sequencing. An improved synthesis of protected deoxynucleoside H-phosphonates is also described.

Nucleoside h-phosphonates: Valuable intermediates in the synthesis of deoxyoligonucleotides

Abstract Nucleoside H-Phosphonates are used directly in the synthesis of H-phosphonate linked deoxyoligonucleotides. A rapid and simplified procedure for the synthesis of deoxyoligonucleotides is described.

Oligodeoxynucleotides containing C-5 propyne analogs of 2'-deoxyuridine and 2'-deoxycytidine

Abstract Oligodeoxynucleotides (ODN) containing 5-(1-propynyl)-2′-deoxyuridine and 5-(1-propynyl)-2′-deoxycytidine significantly enhance double-helix formation with single strand RNA and 5-(1-propynyl)-2′-deoxyuridine significantly enhances triple-helix formation with double stranded DNA.

Deoxynucleoside H-Phosphonate diester intermediates in the synthesis of internucleotide phosphate analogues

Abstract Polymer bound deoxynucleoside H-phosphonate diesters are used as precursors to phosphoramidate, thiophosphate and phosphate triester analogues of DNA.

Substituted 5-phenyltetrazoles: improved activators of deoxynucleoside phosphoramidites in deoxyoligonucleotide synthesis

Abstract 5-(p-nitrophenyl)tetrazole, a tetrazole of enhanced acidity relative to 5-H-tetrazole, is a superior activator of the N-morpholinophosphoramidite in the synthesis of deoxyoligonucleotides.

Deoxyoligonucleotides with Inverted Polarity Synthesis and Use in Triple-Helix Formation

Abstract Deoxyoligonucleotides with inverted polarity (containing a 3′-3′ junction) are described. The ability of these oligonucleotides to bind to duplex DNA utilizing various linker elements is discussed.

Oligonucleotides derived from 5-(1-propynyl)-2′-O-allyl-uridine and 5-(1-propynyl)-2′-O-allyl-cytidine: Synthesis and RNA duplex formation

The protected nucleoside analogs of 5-(1-propynyl)-2′-O-allyl-uridine and 5-(1-propynyl)-2′-O-allyl-cytidine are described. Oligonucleotides containing this modification significantly enhance double-helix formation with single-strand RNA.

Development of Antisense Therapeutics: Implications for Cancer Gene Therapy

Gene inhibition by antisense oligodeoxynucleotides (ODNs) has been documented for numerous oncogenes important in human cancers.*.2 Many of the early studies led to speculation on the use of antisense ODNs in therapies. Unfortunately, more recent studies appear to indicate that much of the activity attributed to an antisense mechanism is due to a nonspecific and non-antisense mechanism of Advances in the antisense field will require new modifications that enhance cellular permeation, affinity, and stability of ODNs.

Oligodeoxynucleotides containing 5-(1-propynyl)-2'-deoxyuridine formacetal and thioformacetal dimer synthons

Abstract Oligodeoxynucleotides containing the C-5 propyne 2′-deoxyuridine analog in conjunction with the formacetal and 3′-thioformacetal linkage are described. Thermal denaturation analysis demonstrates that these analogs have enhanced binding affinity to both single-strand RNA and DNA and double-strand DNA.

The Use of Nucleoside H-Phosphonates in the Synthesis of Deoxyoligonucleotides

Abstract Nucleoside H-phosphonates are valuable intermediates in the synthesis of deoxyoligonucleotides. The DBU salt form is more stable in solution and is consequently an improvement in routine synthesis of DNA.