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• W1970252085 endingPage "1607" @default.
• W1970252085 startingPage "1600" @default.
• W1970252085 abstract "A new upper limit of binding site size is defined for the 2:1 overlapped polyamide: DNA motif. Eight-ring polyamides composed of four-ring subunits containing pyrrole (Py) and imidazole (Im) amino acids linked by a central β-alanine (β) spacer („4-β-4 ligands”︁) were designed for recognition of eleven base pair sequences as antiparallel dimer (4-β-4)2.DNA complexes in the minor groove. The DNA binding properties of three polyamides, ImPyPyPy-β-PyPyPyPy-β-Dp, ImImPyPy-β-PyPyPyPy-β-Dp, and ImImImPy-β-PyPyPyPy-β-Dp, were analyzed by footprinting experiments on DNA fragments containing the respective match sites 5'-AGTAATTTACT-3', 5'-AGGTATTACCT-3', and 5'-AGGGATTCCCT-3' (Dp = dimethylaminopropylamide). Quantitative footprint titrations reveal that each polyamide binds its respective target site with subnanomolar affinity and 7-fold to over 30-fold specificity over double-base-pair mismatch sites. A 20-fold decrease in binding affinity is observed for placement of a side-by-side β-β pairing opposite G.C/C.G relative to placement opposite a A.T/T.A base pair. The use of side-by-side antiparallel β-alanine residues as an A.T/T.A-specific DNA binding element provides a new pairing rule for polyamide design. Expanding the DNA binding site size targeted by pyrrole-imidazole polyamides represents an important step in the development of cell-permeable synthetic ligands for the control of gene-specific regulation." @default.
• W1970252085 created "2016-06-24" @default.
• W1970252085 creator A5014051252 @default.
• W1970252085 creator A5021604462 @default.
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• W1970252085 date "1997-10-01" @default.
• W1970252085 modified "2023-09-27" @default.
• W1970252085 title "A Pyrrole-Imidazole Polyamide Motif for Recognition of Eleven Base Pair Sequences in the Minor Groove of DNA" @default.
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• W1970252085 doi "https://doi.org/10.1002/chem.19970031009" @default.
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