title: Binding affinity and mode of distamycin A with A/T stretches in double-stranded DNA: importance of the terminal A/T residues.
abstract: Distamycin A (Dst) is an antibiotic which binds to the minor groove of double-stranded DNA at A/T-rich regions. We have examined the affinity and mode of Dst binding to DNA duplexes containing a conserved A/T core and variable terminal A/T regions by using circular dichroism spectroscopy. The observed circular dichroism spectra were analyzed by singular value decomposition and fitted to a two-step binding model. The result clearly shows a correlation between the affinity for Dst and the preference for Dst-DNA 1:1 binding over 2:1 binding. The A/T stretches that prefer 1:1 binding form high-affinity 1:1 complexes, whereas those preferring 2:1 binding form stable 2:1 complex with low overall affinities. The terminal A/T residues of the Dst binding region play an important role in the stabilization/destabilization of the 1:1 and 2:1 complexes, resulting in a terminal residue-dependent variation of the binding affinity and the binding mode preference.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Tohoku University, Aobayama, Sendai 980-8578, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Asagi
authors.forename: Akira
authors.initials: A
authors.lastname: Toyama
authors.forename: Hideo
authors.initials: H
authors.lastname: Takeuchi
mesh_terms: D000225:Adenine / Q000737:chemistry*; D000998:Antiviral Agents / Q000737:chemistry*; D001665:Binding Sites; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry*; D004214:Distamycins / Q000737:chemistry*; D013941:Thymine / Q000737:chemistry*
chemical_list: D000998:Antiviral Agents; D004214:Distamycins; C030000:stallimycin; D004247:DNA; D000225:Adenine; D013941:Thymine