Is ligation the only solution to the pyrophosphate problem?

Abstract

Pyrophosphate linkages are easily formed during the nonenzymatic oligomerization of activated nucleotides. They often form `caps' which terminate an oligonucleotide with a 5'-5' pyrophosphate. Owing to their structural resemblance to the intermediates in enzymatic ligation reactions, it has been suggested that pyrophosphate caps might have been capable of acting as activating groups in chain elongation processes. We argue that an alternative possibility would have been the specific hydrolysis of pyrophosphates.