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Published November 4, 1992 | public
Journal Article

Design of peptides that bind in the minor groove of DNA at 5'-(A,T)G(A,T)C(A,T)-3' sequences by a dimeric side-by-side motif

Abstract

The designed peptides pyridine-2-carboxamide-netropsin (2-PyN) and 1-methylimidazole-2-carboxamide-netropsin (2-ImN) are crescent-shaped synthetic analogs of the natural products netropsin (N) and distamycin A (D). Footprinting experiments indicate that the peptides 2-PyN and 2-ImN bind specifically the 5 base pair sequence 5'-TGTCA-3'. Affinity cleaving data suggest that the complexes, 2-ImN.5'-TGTCA-3' and 2-PyN.5'-TGTCA-3', are composed of two equivalent orientations which disfavor a 1:1 model. The footprinting and affinity cleaving data are in accord with a 2:1 complex where a novel side-by-side antiparallel dimer binds in the minor groove of double-helical DNA.

Additional Information

© 1992 American Chemical Society. Received May 11, 1992. Publication Date: November 1992. We are grateful to the National Institutes of Health (GM-27681) and to Burroughs Wellcome for research support, to the National Science Foundation for a predoctoral fellowship to W.S.W., and to the National Institutes of Health for a Research Service Award to M.M.

Additional details

Created:
August 20, 2023
Modified:
October 18, 2023