(294i) Investigation on the Selective Interactions Between Flouroquinolonyl-Ampicillin Derivative and Double Stranded Oligonulceotides

Corresponding Author: Yu Tien Liu, Institute of Microbiology and Immunology, National Defense Medical Center, P.O. Box 90048-505, Ndihu, Taipei 114, Taiwan, Republic of China. Phone: 886-2-87924958, Fax: 886-2-87923151, e-mail: ytliu@ndmctsgh.edu.tw

Abstract The synthesized compound N-(6-fluoroquinoloyl)-ampicillin(FQ-1) exhibits a broad-spectrum on biological effects against bacteria, protozoa, virus and cancer cells. From the results of the migration shift of eight kinds oligonucleotides on agarose electrophoresis, it revealed that FQ-1 could intercalate into double-stranded DNA but not single-stranded DNA, the GC contents is needed, and two tandem GC sequence was the minimal requirement for intercalation. Complexes of FQ1 with 8mer of GC and CG, as double stranded oligonucleotides, were formed in solution and analyzed by electrospray ionization mass spectrometry (ESI-MS). A full-scan mass spectra suggests that the specific binding only happened with 5'-d(GCGCGCGC)2-3', supported by the complex ion peak at 1471, along with the helix ion at 1206. Two molecules of FQ1 were binding on this specific lined 8mer. The results shown that FQ1 is preferentially a GC sequence selector in 2:1 complexes with ds (GC)4 oligomers. This orientation specificity deserve further study about the three dimension topology of its relation with stoichiometry. The sequence selectivity might offers main effects on its activity against Vaccinia virus replication, a double- stranded DNA virus and lower cytotoxicity to BHK 21 is considered.

KEY WORDS: Flouroquinolonyl-penicillin, Oligonucleotide, biding specificy, antivirus drugs, electrospray ionization mass spectrometry