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Methionine Functionalized Biocompatible Block Copolymers for Targeted Plasmid DNA Delivery
Published on: August 6, 2019
Hairpin versus extended DNA binding of a substituted beta-alanine linked polyamide
Craig R Woods1, Takahiro Ishii, Bing Wu
1Department of Chemistry and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Abstract:
A series of alpha-substituted beta-alanine (beta) linked polyamides (DbaPyPyPy-beta*-PyPyPy) were prepared and examined. This resulted in the observation that while most substituents disrupt DNA binding, (R)-alpha-methoxy-beta-alanine (beta((R)-OMe)) maintains strong binding affinity and preferentially adopts a hairpin versus extended binding mode, providing an alternative hairpin linker to gamma-aminobutyric acid (gamma). A generalized variant of a fluorescent intercalator displacement assay conducted on a series of hairpin deoxyoligonucleotides containing a systematically varied A/T-rich binding site size was developed to distinguish between the extended binding of the parent beta-alanine 1 (DbaPyPyPy-beta-PyPyPy) and the hairpin binding of 3 (DbaPyPyPy-beta((R)-OMe)-PyPyPy).
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