title: Influence of linker length in shape recognition of B* DNA by dimeric aminoglycosides.
abstract: DNA-protein recognition has shown us the importance of DNA shapes in the recognition process. Specific high-affinity targeting of DNA shapes by small molecules is desirable for many biological applications that involve regulation of DNA based processes. Here, the effect of linker length and rigidity on the affinity of a conjugated neomycin dimer for a specific DNA shape (B* form) AT-rich DNA was explored. Binding constants approximating 10(8)M(-1) for optimal linker lengths of 18-19 atoms are reported herein.
authors.affiliation: Laboratory of Medicinal Chemistry, Department of Chemistry, Clemson University, Clemson, SC 29634, United States.
authors.forename: Sunil
authors.initials: S
authors.lastname: Kumar
authors.affiliation: NUBAD, LLC, 900 B West Faris Road, Greenville, SC 29605, United States.
authors.forename: Meredith Newby
authors.initials: MN
authors.lastname: Spano
authors.affiliation: Laboratory of Medicinal Chemistry, Department of Chemistry, Clemson University, Clemson, SC 29634, United States. Electronic address: dparya@clemson.edu.
authors.forename: Dev P
authors.initials: DP
authors.lastname: Arya
mesh_terms: D020856:AT Rich Sequence; D001665:Binding Sites; D059371:DNA, B-Form / Q000737:chemistry*; D019281:Dimerization; D007700:Kinetics; D009355:Neomycin / Q000031:analogs & derivatives / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D059371:DNA, B-Form; D009355:Neomycin
keywords: Aminoglycoside derivatives; Fluorescent intercalator displacement; Isothermal calorimetry titration; Major groove binders; Nucleic acid