Synthesis and NMR binding study of a chiral spirocyclic helical analogue of a natural DNA bulge binder.
[reaction: see text] Synthesis of chiral spirocyclic helical compounds which mimic the molecular architecture of the potent DNA bulge binder obtained from the antitumor agent NCS-chrom has been accomplished. Structural analysis of the compounds by CD and NMR is presented. NMR titration study indicates binding of P,alpha-helimer (1d) at a two-base bulge site in a DNA oligomer, providing insight to the design of agents as specific probes of a bulged structure in nucleic acids.
Gaikwad
Nilesh W
NW
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Hwang
Geum-Sook
GS
Goldberg
Irving H
IH
D003500:Cyclization; D004247:DNA / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008958:Models, Molecular; D008968:Molecular Conformation; D009841:Oligonucleotides / Q000737:chemistry; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
D009841:Oligonucleotides; D013141:Spiro Compounds; D004247:DNA