In collaboration with B. Han, Swiss Federal Institute of Technology, Zürich, Switzerland, we developed the triazination of the carboxyl group of a variety of α-amino acids such as glycine, serine, cysteine, aspartic acid, glutamic acid, β-amino-alanine, and α-carboxy-glycine to produce correspondingly triazine-tagged building blocks of potentially informational oligomers.
Oligomers Based On Triazine-Tagged Backbones
Of the 2 planned variants (compounds 1 and 2 in Fig. 1) of ethylenediamine-based oligomer systems containing triazine as recognition elements, we were able to synthesize and study oligomers (up to dodecamer) of 1 of them (2 in Fig. 1). As expected, oligomers of this chemical structure underwent efficient cross-pairing with polyuracil (RNA) and polythymine (DNA) (Table 1). However, to our surprise, the backbones of oligomers of this type were unstable because of a triazine-assisted eliminative fragmentation.
A comparative conformational analysis
relative to RNA (tagged with the conventional nucleobases) of oligomer backbones tagged with
triazines predicted that oligodipeptides of type 2 and 4 (Fig. 1) might be oligomer
systems that cross-pair with RNA, whereas oligopeptides of type 3 should not (or less efficiently
so). Experimental results obtained so far are in accord with the analysis, except that oligopeptides
of type 3 also cross-pair with RNA, yet much more weakly than those of type 4 do (Table
1). The oligopeptides of type 4, composed of a triazine-tagged oligomer consisting of
alternating glutamic and aspartic acid residues, cross-pairs with RNA (polyuracil) strongly
(Table 1). Studies on the self-pairing and cross-pairing properties of type 4 are under
A variation of oligodipeptide system 3 is the oligodipeptoid of the type 5 (Fig. 1), constructed from the iminodiacetic acid unit, wherein the triazine- and carboxylate-containing side chains are now appended to the nitrogen atoms along the backbone, making this system achiral. We used a solid-support strategy starting from the requisite monomers to synthesize oligomers (up to dodecamer). The resultant oligodipeptoids cross-paired with RNA (polyuracil) and DNA (polythymine) (Table 1).
Ferencic, M., Reddy, G., Wu, X., Guntha, S.G., Nandy, J., Krishnamurthy, R., Eschenmoser, A. Base-pairing systems related to TNA containing phosphoramidate linkages: synthesis of building blocks and pairing properties. Chem. Biodivers. 1:939, 2004.
Han B., Jaun, B., Krishnamurthy, R., Eschenmoser, A. Mannich type C-nucleosidations in the 5,8-diaza-7,9-dicarba-purine family. Org. Lett. 6:3691, 2004.
Han, B., Rajwanshi, V., Nandy, J., Krishnamurthy, R., Eschenmoser, A. Mannich-type C-nucleosidations with 7-carba-purines and 4-amino-pyrimidines. Synlett 744, 2005, Issue 4.