Sequential ligation

The first theory is that life started as a self replicating RNA single strand, that lined up free nucleotides and ligated sequentially in proper 3 -5 phosophodiester bonds, then the two strands would separate and cycle. This theory, obviously driven by the symmetry of double stranded DNA and RNA helices, has not yet worked (7). 

Wu, D and Wallace, R. (1989). The ligation amplification reaction (LAR)—amplification of specific DNA sequences using sequential rounds of template dependent ligation. Genomics 4,560-569. 

A consideration in a tandem strategy is the choice of two pairs of nucleophiles and electrophiles to achieve the reaction sequences of cyclization and convergent ligation. One entire pair essential for the cyclization reaction is placed in the peptide precursor, while the other pair for the convergent ligation is split between the peptide and the core. Although various combinations of these pairs can be exploited for the sequential reactions in thiol and... 

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