Javier Ellena -        From Rational Design of Drug Crystals to Understanding of Nucleic Acid Structures: Lamivudine Duplex

Version 1

      Publication Details (including relevant citation   information):

        Martins, Felipe T., Doriguetto, Antonio C., Ellena, Javier

      CRYSTAL GROWTH & DESIGN, Volume: 10, Issue: 2, Pages:   676-684,Published: FEB 2010

      Abstract:

      Abstract: A DNA-like duplex of nucleosides is probable to exist   even without the 5'-phosphate groups needed to assemble the chain   backbone. However, double-stranded helical structures of   nucleosides are unknown. Here, we report a duplex of nucleoside   analogs that is spontaneously assembled due to stacking of the   neutral and protonated molecules of lamivudine, a nucleoside   reverse transcriptase inhibitor (NTRI) widely used in anti-HIV   drug combinatory medication. The left-handed lamivudine duplex   has features similar to those of i-motif DNA, as the face-to-face   base stacking and the helix rise per base pair. Furthermore, the   protonation pattern on alternate bases expected for it DNA-like   duplex stabilized by pairing of neutral and protonated cytosine   fragments was observed for the first time in the lamivudine   double-stranded helix. This structure demonstrates that hydrogen   bonds can substitute for covalent phosphodiester linkage in the   stabilization of the duplex backbone. This interesting example of   spontaneous molecular self-organization indicates that the   5'-phosphate group could not be a requirement for duplex   assembly.

      Co-Authors:
      javiere@ifsc.usp

      Address (URL): http://pubs.acs.org/doi/abs/10.1021/cg901103r