Recognition of nine base pair sequences in the minor groove of DNA at subpicomolar concentrations by a novel microgonotropen.
The dsDNA interactions of the novel microgonotropen L1 have been characterized via spectrofluorometric titrations and thermal melting studies. A microgonotropen consists of a DNA minor groove binding moiety attached to a basic side chain capable of reaching out of the minor groove and grasping the acidic DNA phosphodiester backbone. L1 was synthesized employing solid-phase chemistry. L1 is shown to distinguish nine base pair A/T rich binding sites from sites possessing fewer than nine contiguous A/T base pairs. Further, L1 binds its preferred dsDNA sequences at subpicomolar concentrations. The equilibrium constant for complexation (K(1)) of a nine base pair A/T rich dsDNA binding site by L1 is roughly 10(13) M(-1). Single base pair A/T --> G/C substitutions within the nine base pair A/T rich binding site of L1 decreases the equilibrium constant for DNA binding by 1-2 orders of magnitude. The three proplyamine side chains of L1 enhance the agents free energy of binding by more than 5 kcal. Molecular modeling suggests that L1 adopts a 'spiral-like' conformation which fits almost a full turn of the DNA helix.
Satz
Alexander L
AL
Department of Chemistry and Biochemistry, University of California, Santa Barbara, CA 93106, USA.
Bruice
Thomas C
TC
D020029:Base Pairing; D001483:Base Sequence; D001562:Benzimidazoles / Q000737:chemistry* / Q000378:metabolism*; D001665:Binding Sites; D001671:Biochemistry / Q000379:methods; D004247:DNA / Q000737:chemistry* / Q000378:metabolism*; D004214:Distamycins / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D009692:Nucleic Acid Heteroduplexes; D011758:Pyrroles / Q000737:chemistry* / Q000378:metabolism*; D016385:TATA Box
D001562:Benzimidazoles; D004214:Distamycins; D009692:Nucleic Acid Heteroduplexes; D011758:Pyrroles; C452299:microgonotropen L1; C437884:microgonotropen L2; D004247:DNA