Hairpin versus extended DNA binding of a substituted beta-alanine linked polyamide.
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).
Woods
Craig R
CR
Department of Chemistry and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Ishii
Takahiro
T
Wu
Bing
B
Bair
Kenneth W
KW
Boger
Dale L
DL
D000409:Alanine / Q000737:chemistry*; D003432:Cross-Linking Reagents / Q000737:chemistry; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D007364:Intercalating Agents / Q000737:chemistry; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D009757:Nylons / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism
D003432:Cross-Linking Reagents; D007364:Intercalating Agents; D009757:Nylons; D011758:Pyrroles; D004247:DNA; C096654:N-methylpyrrole; D000409:Alanine