Enzymatic nucleic acid synthesis: compositions and methods for inhibiting pyrophosphorolysis

A method for sequencing nucleic acids, comprising:

• a) flowing labeled deoxynucleotide triphosphates and modified pyrophosphates onto template nucleic acids which are hybridized to a primer nucleic acid, where the template nucleic acids or primers are attached to a support, and wherein the labeled nucleotide triphosphates include a molecular tag bonded to the beta- or gamma-phosphate, wherein the molecular tag emits a detectable signal, and wherein the modified pyrophosphates include at least one compound selected from the group consisting of compound having the following general formulas
• Z—OPO2—(OP(EE′)O)n—PO2O—Z′ (i)
• Z—OPO2—(OP(EE′)O)nPO2—Z′ (ii)
• Z—PO2—(OP(EE′)O)nPO2O—Z′ (iii)
• Z—PO2—(OP(EE′)O)nPO2—Z′ (iv)
• where Z and Z′ are each independently a hydrogen atom, E and E′ are each independently an oxygen atom and n is an integer having a value of 2, 3, 4 or 5;
• b) incorporating one of the labeled nucleotide triphosphates into at least one of the primers with a polymerase;
• c) releasing a tagged pyrophosphate which includes the molecular tag bonded to the beta- or gamma-phosphate;
• and
• d) detecting the released tagged pyrophosphates.