Proposed mechanism of amino acid-catalysed RNA oligomerisation. In the dry state, due to the proximity and orientation effects, the amine group of the amino acid (1) may act as a general base to facilitate proton transfer from the 5'-OH of the nucleotide, which attacks the cyclic phosphate of a second nucleotide whilst the ammonium moiety of zwitterionic amino acid (1*, protonated form of 1), may act as a general acid to facilitate proton transfer to the 2'-OH or 3'-OH. Acid-base catalysis can also be achieved by nucleobases, such as guanine (2 and its protonated form 2*) or uracil, as they both have pKa values close to the amine pKaH of the amino acids. The mechanism in the opposite direction can be followed for acid-base-catalysed RNA fragmentation 13 .
