Abstract：
:Polyamides composed of N-methylpyrrole (Py) and N-methylimidazole (Im) subunits can bind in the minor groove of DNA at predetermined sequences with subnanomolar affinity and high specificity. Covalent linkage of polymer subunits using a gamma-aminobutyric acid linker has been shown to increase both the affinity and specificity of polyamides. Using a fluorescence detected stopped-flow assay, we have studied the differences in association and dissociation kinetics of a series of polyamides representing unlinked, hairpin and cyclic analogues of the four ring polyamide ImPyPyPy-beta-Dp. Whereas the large differences seen in the equilibrium association constants between the unlinked and covalently linked polyamides are primarily due to higher association rate constants, discrimination between matched and mismatched sites by each polyamide can be ascribed in large part to differences in their dissociation rate constants. The consequences of this kinetic behavior for future design are discussed.
journal_name
Biochemistryjournal_title
Biochemistryauthors
Baliga R,Baird EE,Herman DM,Melander C,Dervan PB,Crothers DMdoi
10.1021/bi0022339subject
Has Abstractpub_date
2001-01-09 00:00:00pages
3-8issue
1eissn
0006-2960issn
1520-4995pii
bi0022339journal_volume
40pub_type
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