Rational design and synthesis of a double-stranded DNA-binder library.
Described is a computer-assisted rational design of a DNA-bis-intercalator peptide library. The peptide library of 250 members was prepared and the most powerful binder identified. A value of the binding constant is almost two orders of magnitude higher than that of starting building block-9-aminoacridine. The binder affinity found toward calf thymus DNA is 30-fold of that of human prion peptide 106-126.
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, 166 10 Prague 6, Czech Republic.
Jaroslav
J
Sebestík
Jan
J
Hlavácek
Ivan
I
Stibor
D000585:Aminacrine / Q000737:chemistry; D000818:Animals; D002417:Cattle; D020650:Combinatorial Chemistry Techniques; D017076:Computer-Aided Design; D004247:DNA / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D005456:Fluorescent Dyes / Q000737:chemistry; D015723:Gene Library; D006801:Humans; D007364:Intercalating Agents / Q000737:chemistry; D008958:Models, Molecular; D010446:Peptide Fragments / Q000378:metabolism; D011328:Prions / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013950:Thymus Gland / Q000737:chemistry
D004268:DNA-Binding Proteins; D005456:Fluorescent Dyes; D007364:Intercalating Agents; D010446:Peptide Fragments; D011328:Prions; C082632:prion protein (106-126); D000585:Aminacrine; D004247:DNA