Synthesis of Acyclothymidine Triphosphate and α-<i>P</i>-Boranotriphosphate and Their Substrate Properties with Retroviral Reverse Transcriptase

Li, Ping; Dobrikov, Mikhail I.; Liu, Hongyan; Shaw, Barbara Ramsay

doi:10.1021/ol034538w

Cited by 17 publications

(18 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similar results have been obtained for incorporation of acycloTTPαB by MMLV RT 71. Thus, BP substitution in ddNTPs indeed results in selective increase in efficiency of incorporation by viral RTs, whereas it decreases the efficiency of incorporation for the BP chain terminator by bacterial DNA polymerases 70…”

Section: Potential Genomic and Therapeutic Applications Of Boranophossupporting

confidence: 81%

“…On the basis of these data we synthesized boranophosphate 2′,3′‐dideoxy‐(dd)70 and acycloNTP71 analogs. Steady‐state and presteady kinetic analyses indicate that, whereas the efficiency of the single nucleotide incorporation for ddCTP by MMLV RT is nearly two orders lower than for natural dCTP, the introduction of an α‐ P ‐borano group increases the efficiency of incorporation for ddCTPαB by 30‐fold 70. Similar results have been obtained for incorporation of acycloTTPαB by MMLV RT 71.…”

Section: Potential Genomic and Therapeutic Applications Of Boranophossupporting

confidence: 73%

“…Thus, an α‐boranophosphate group in dNTPs increases their selectivity to viral RTs relative to bacterial DNA polymerases. On the basis of these data we synthesized boranophosphate 2′,3′‐dideoxy‐(dd)70 and acycloNTP71 analogs. Steady‐state and presteady kinetic analyses indicate that, whereas the efficiency of the single nucleotide incorporation for ddCTP by MMLV RT is nearly two orders lower than for natural dCTP, the introduction of an α‐ P ‐borano group increases the efficiency of incorporation for ddCTPαB by 30‐fold 70.…”

Section: Potential Genomic and Therapeutic Applications Of Boranophosmentioning

confidence: 99%

See 2 more Smart Citations

Reading, Writing, and Modulating Genetic Information with Boranophosphate Mimics of Nucleotides, DNA, and RNA

Shaw

Dobrikov

Wang

et al. 2003

Annals of the New York Academy of Sciences

Self Cite

View full text Add to dashboard Cite

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 (-BH3) 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 alpha-P-borano nucleoside triphosphate analogs (e.g., NTPalphaB and dNTPalphaB). The NTPalphaB and dNTPalphaB 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-NTPalphaB 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.

show abstract

Section: Potential Genomic and Therapeutic Applications Of Boranophossupporting

confidence: 81%

Section: Potential Genomic and Therapeutic Applications Of Boranophossupporting

confidence: 73%

Section: Potential Genomic and Therapeutic Applications Of Boranophosmentioning

confidence: 99%

See 1 more Smart Citation

Reading, Writing, and Modulating Genetic Information with Boranophosphate Mimics of Nucleotides, DNA, and RNA

Shaw

Dobrikov

Wang

et al. 2003

Annals of the New York Academy of Sciences

Self Cite

View full text Add to dashboard Cite

show abstract

“…Nucleic acid boranophosphates were pioneered by Shaw,11 and they are receiving increasing attention for therapeutics and diagnostics 12-14. Thiophosphates are well known to display altered interactions with other species, including metals 15.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of boranoate, selenoate, and thioate analogs of AZTp4A and Ap4A

et al. 2009

View full text Add to dashboard Cite

We report efficient, one-flask procedures for the synthesis of a family of fourteen analogs of AZTp 4 A and Ap 4 A containing BH 3 , S, or Se, along with two bisphosphonate analogs of Ap 4 A. These compounds should slow unwanted enzymatic hydrolysis and have the potential to create unique binding interactions in biochemical and structural studies of the excision reaction responsible for resistance of HIV-1 to AZT, as well as assist in drug design.

show abstract

“…In nature, pyrazines are enzymatically produced through amino acids, and they are common units of a great variety of natural marine products with cytotoxic and antitumor properties [6][7][8]. In the production of potassium Clavulanate, an important b-lactamases inhibitor is necessary to account for standards of some pyrazines to determine and prove the purity level of the pharmaceutical drug; as a consequence, the synthesis of these heterocycles, therefore, is required [9].…”

Section: Introductionmentioning

confidence: 99%