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Published April 23, 1996 | public
Journal Article

Incorporation of a Non-Nucleotide Bridge into Hairpin Oligonucleotides Capable of High-Affinity Binding to the Rev Protein of HIV-1

Abstract

A bridge containing a rigid trans-stilbene group, −P(O)(O-)O(CH_2)_3NHC(O) C_6H_4CH CHC_6H_4C(O)NH(CH_2)_3OP(O)(O-)−, has been incorporated into several oligonucleotide sequences based on the minimal Rev Binding Element (RBE) of HIV-1. This bridge was found to be as effective as a UUCG tetraloop in stabilizing short RNA duplex structures containing mismatched bases and bulged out nucleotide residues and to be more effective than either a TTTT loop or a triethyleneglycol linker in stabilizing similar DNA structures. Evaluation of stilbene-containing RNA RBE sequences of varying length for their ability to bind the Rev protein of HIV-1 showed that a 22-nucleotide stilbenedicarboxamide conjugate bound Rev almost as well as a 94-base fragment of the Rev Responsive Element (RRE). A DNA hairpin mimetic with the same sequence was incapable of Rev binding. Taken together, these experiments serve as an example for how in vitroselection and chemical modification can be combined to generate high-affinity mimetics of nucleic acid sequence and structure.

Additional Information

© 1996 American Chemical Society. Received December 11, 1995; Revised Manuscript Received February 14, 1996. This research was supported by grants from the National Institutes of Health, UOI AI24846 and AI-36083, and by an NSF National Young Investigator Award (A.E.), a Scholar Award from the American Foundation for AIDS Research (A.E.), and The Pew Scholar Award in the Biomedical Sciences (A.E.). Rev protein was a generous gift of Dr. Maria Zapp.

Additional details

Created:
August 20, 2023
Modified:
October 17, 2023