The tripler forming ability of nonnatural nucleobases: a computational approach

Nucleotide bases with the capability of specific H-bonding interactions wit h base pairs in the major groove of DNA have been designed. During the proc edure several factors were taken into account: the molecule (i) should cont ain substructure capable of Hoogsteen H-bonding with the purine base of the Watson-Crick doublet; (ii) should be cyclic and planar; (iii) for practica l purposes it should be chemically stable; and (iv) the triplet should also be stable. Calculations by semiempirical methods lead to four compounds as possible triplet forming nucleobases: quinolin-2-ylamine, indol-2-ylamine, pyridin-2-ylamine and 2-aminopyrrol. They all meet the above criteria. Geo metry optimization of the triplets resulted in H-bond distances as well as H-bond energies. (C) 2000 Elsevier Science B.V. All rights reserved.