Interactions of multicationic bis(guanidiniocarbonylpyrrole) receptors with double-stranded nucleic acids: syntheses, binding studies, and atomic force microscopy imaging.
Compounds 1-3, composed of two guanidiniocarbonylpyrrole moieties linked by oligoamide bridges and differing in number and type of basic groups, were prepared. The sites and degree of protonation of 1-3 depend strongly on the pH value. The interactions of these compounds with several double-stranded (ds) DNA and dsRNA were investigated by means of UV/Vis and CD spectroscopy as well as isothermal titration microcalorimetry (ITC). These studies revealed that the binding of 1-3 to the polynucleotides is driven by three factors, the presence of aliphatic amino groups, the protonation state of the compounds, and the steric properties of the polynucleotide binding site, that is, the shape and structure of their grooves. The results obtained by all applied methods consistently indicated that receptors 1-3 bind to the minor groove of DNA, but, by contrast, to the major groove of RNA. Additionally, it was shown by atomic force microscopy (AFM) imaging that upon interaction of compound 2 with calf thymus (ct) DNA induced aggregation of the DNA occurs, leading to pronounced changes in its secondary structure.
Institute for Organic Chemistry, University of Duisburg-Essen, Universitätsstrasse 7, 45141 Essen, Germany.
Karsten
K
Klemm
Marijana
M
Radić Stojković
Gordan
G
Horvat
Vladislav
V
Tomišić
Ivo
I
Piantanida
Carsten
C
Schmuck
D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D006146:Guanidines / Q000138:chemical synthesis / Q000737:chemistry*; D018625:Microscopy, Atomic Force; D008956:Models, Chemical; D015394:Molecular Structure; D011119:Polynucleotides / Q000737:chemistry; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry*; D012330:RNA, Double-Stranded / Q000737:chemistry* / Q000378:metabolism
D006146:Guanidines; D011119:Polynucleotides; D011758:Pyrroles; D012330:RNA, Double-Stranded; D004247:DNA; C427203:calf thymus DNA