title: Design of stapled DNA-minor-groove-binding molecules with a mutable atom simulated annealing method.
abstract: We report the design of optimal linker geometries for the synthesis of stapled DNA-minor-groove-binding molecules. Netropsin, distamycin, and lexitropsins bind side-by-side to mixed-sequence DNA and offer an opportunity for the design of sequence-reading molecules. Stapled molecules, with two molecules covalently linked side-by-side, provide entropic gains and restrain the position of one molecule relative to its neighbor. Using a free-atom simulated annealing technique combined with a discrete mutable atom definition, optimal lengths and atomic composition for covalent linkages are determined, and a novel hydrogen bond 'zipper' is proposed to phase two molecules accurately side-by-side.
authors.affiliation: Department of Biomathematics, University of California, Los Angeles 90024, USA.
authors.forename: W L
authors.initials: WL
authors.lastname: Walker
authors.forename: M L
authors.initials: ML
authors.lastname: Kopka
authors.forename: R E
authors.initials: RE
authors.lastname: Dickerson
authors.forename: D S
authors.initials: DS
authors.lastname: Goodsell
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D004247:DNA / Q000737:chemistry* / Q000648:ultrastructure; D004214:Distamycins / Q000737:chemistry; D019277:Entropy; D006860:Hydrogen Bonding; D006878:Hydroxides; D009429:Netropsin / Q000031:analogs & derivatives / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D004214:Distamycins; D006878:Hydroxides; C053654:lexitropsin; D009429:Netropsin; C030000:stallimycin; D004247:DNA