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.

New 5'-(P a -boronated) analogues of the naturally occurring nucleoside diphosphates ADP and GDP were synthesized in good yields, i.e., adenosine 5'-(P a -boranodiphosphate) (ADPaB; 5a) and guanosine 5'-(P aboranodiphosphate) (GDPaB; 5b). Their diastereoisomers were successfully separated by reversed-phase HPLC, and chemical structures were established via spectroscopic methods. The isoelectronic substitution of borane (BH 3 ) for one of the non-bridging O-atoms in phosphate diesters should impart an increase in lipophilicity and change in polarity in ADPaB and GDPaB. The boronated nucleoside diphosphates could be employed for investigations of the stereochemical course and metal requirements of enzymatic reactions involving ADP and GDP, and as carriers of 10 B in boron neutron-capture therapy (BNCT) for the treatment of cancer.

Four different types of boron-modified nucleotides are reported: P-boranophosphorothioates, P-cyanoboranophosphates, P-boranomethylphosphonates, and P3'-N5'-boranophosphoramidates. Synthesis of dinucleoside borano-phosphorothioates and nucleoside P-borano-P-thiomonophosphates via a lithium sulfide method is described. The Li2S method also provides an alternative way to synthesize phosphorothioates through a dinitrophenyl P(V) phosphotriester precursor. The mechanism of Li2S substitution was investigated.

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