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

Autor(es)

Martins, Felipe T. ^[1] ; Doriguetto, Antonio C. ^[2] ; Ellena, Javier ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Fis Sao Carlos, BR-13560970 Sao Carlos, SP - Brazil

^[2] Univ Fed Alfenas, Dept Ciencias Exatas, BR-37130000 Alfenas, MG - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Crystal Growth & Design; v. 10, n. 2, p. 676-684, FEB 2010.
• Citações Web of Science: 21

Resumo

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. (AU)

• Processo FAPESP: 07/07185-5 - Obtenção, caracterização e avaliação de novas formas cristalinas de fármacos antiretrovirais e antineoplásicos
• Beneficiário: Felipe Terra Martins
• Modalidade de apoio: Bolsas no Brasil - Doutorado