Small changes in cationic substituents of diphenylfuran derivatives have major effects on the binding affinity and the binding mode with RNA helical duplexes.
The interactions of dicationic, 2-4, and tetracationic, 5-7, diphenylfuran analogs of 1 (furamidine) with RNA have been analyzed by thermal melting, spectroscopic, viscometric, kinetic and molecular-modeling techniques. The results of these studies indicate that most of the furan derivatives bind to RNA duplexes by intercalation in contrast to their minor-groove binding mode in AT sequences of DNA, but similar to their binding mode in GC rich regions of DNA. The highest affinity for RNA is found for an imidazoline dication, 2. With some substituents which inhibit formation of a strong intercalation complex, the results suggest a non-intercalative type of binding occurs. The non-intercalative binding probably occurs through a complex with the furan derivative bound in the narrow, deep major groove of A-form RNA helices.
Zhao
M
M
Department of Chemistry, Georgia State University, Atlanta 30303, USA.
Ratmeyer
L
L
Peloquin
R G
RG
Yao
S
S
Kumar
A
A
Spychala
J
J
Boykin
D W
DW
Wilson
W D
WD
D000578:Amidines / Q000737:chemistry*; D000935:Antifungal Agents / Q000737:chemistry* / Q000494:pharmacology; D001550:Benzamidines; D002412:Cations; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry; D008958:Models, Molecular; D011010:Pneumocystis / Q000187:drug effects; D012313:RNA / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013696:Temperature
D000578:Amidines; D000935:Antifungal Agents; D001550:Benzamidines; D002412:Cations; D012313:RNA; C033286:furamidine; D004247:DNA