The interaction of substituted 2-phenylquinoline intercalators with poly(A).poly(U): classical and threading intercalation modes with RNA.
The interaction of a series of 2-phenylquinoline derivatives with RNA was investigated by means of viscometric, pKa, spectroscopic, binding, Tm, and kinetic methods. Compounds 1, 2, and 3 have a piperazyl substituent at the para, meta, or ortho position, respectively, while 4 has an unsubstituted phenyl ring. The pKa results suggest that 1 has three charges, 2 and 3 have more than two charges, and 4 has two charges at pH 6.2. Spectroscopic and Tm results indicate that 1 binds more strongly to RNA than 2-4. Kinetic and modeling results indicate that 1 is a threading intercalator while 2 and 4 are classical intercalators. All experimental results indicate that 3, which has a large twist between the phenyl and quinoline rings, binds weakly with RNA.
Zhao
M
M
Department of Chemistry, Georgia State University, Atlanta 30303.
Janda
L
L
Nguyen
J
J
Strekowski
L
L
Wilson
W D
WD
D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D015497:HIV-1 / Q000187:drug effects; D007364:Intercalating Agents / Q000737:chemistry* / Q000494:pharmacology; D007700:Kinetics; D011063:Poly A-U / Q000737:chemistry*; D011804:Quinolines / Q000737:chemistry / Q000494:pharmacology; D012313:RNA / Q000737:chemistry* / Q000187:drug effects; D012367:RNA, Viral / Q000737:chemistry / Q000187:drug effects
D000998:Antiviral Agents; D007364:Intercalating Agents; D011804:Quinolines; D012367:RNA, Viral; D011063:Poly A-U; D012313:RNA