Abstract: The invention provides a method of nonenzymatic ligation of a nucleic acid. The method consists of contacting a polynucleotide-3? phosphorothiolate with an acceptor polynucleotide under conditions that allow formation of a phosphodiester bond between the polynucleotide-3? phosphorothiolate and the acceptor polynucleotide. The invention also provides methods of molecular cloning. In one embodiment, the method consists of contacting an insert comprising a polynucleotide-3? phosphorothiolate with an acceptor vector under conditions that allow formation of a phosphodiester bond between the insert and the acceptor vector to generate a vector comprising an insert polynucleotide. The invention further provides a compound consisting of a polynucleotide-3? phosphorothiolate and a kit containing a polynucleotide-3? phosphorothiolate. Also provided is a method of ligating a nucleic acid using a non-sequence specific topoisomerase.

Abstract: Novel nucleotide triphosphates, methods of synthesis and process of incorporating these nucleotide triphosphates into oligonucleotides, and isolation of novel nucleic acid catalysts (e.g., ribozymes) are disclosed. Also, described are the use of novel enzymatic nucleic acid molecules to inhibit HER2/neu/ErbB2 gene expression and their applications in human therapy.

Abstract: The invention provides a method of nonenzymatic ligation of a nucleic acid. The method consists of contacting a polynucleotide-3′ phosphorothiolate with an acceptor polynucleotide under conditions that allow formation of a phosphodiester bond between the polynucleotide-3′ phosphorothiolate and the acceptor polynucleotide. The invention also provides methods of molecular cloning. In one embodiment, the method consists of contacting an insert comprising a polynucleotide-3′ phosphorothiolate with an acceptor vector under conditions that allow formation of a phosphodiester bond between the insert and the acceptor vector to generate a vector comprising an insert polynucleotide. The invention further provides a compound consisting of a polynucleotide-3′ phosphorothiolate and a kit containing a polynucleotide-3′ phosphorothiolate. Also provided is a method of ligating a nucleic acid using a non-sequence specific topoisomerase.

Abstract: The invention provides a compound that inhibits the activity of 3′-tyrosyl-DNA phophodiesterase (TDP). In one embodiment, the compound is a polynucleotide-3′-bridging phosphoramidate. The invention also provides a method of inhibiting TDP activity. In one embodiment, the method involves contacting the enzyme with a polynucleotide-3′-bridging phosphoramidate, polynucleotide-3′-alkyl phosphonate, polynucleotide-3′-alkyl phosphotriester, polynucleotide-bridging-alkyl phosphonate, nucleotide-3′-bridging phosphoramidate, nucleotide-3′-alkyl phosphonate, nucleotide-3′-alkyl phosphotriester, or nucleotide-bridging-alkyl phosphonate. The invention further provides a method of decreasing cellular proliferation. The method involves contacting a TDP-containing cell with an effective amount of a TDP inhibiting compound sufficient to inhibit TDP activity in said cell. In addition, the invention provides a method of screening for compounds that modulate the activity of TDP.