Preparation of stilbene-tethered nonnatural nucleosides for use with blue-fluorescent antibodies.
The synthesis of the first examples of stilbene-tethered hydrophobic C-nucleosides is described. Compounds of this type are targeted for use with our recently reported "blue-fluorescent antibodies" with the aim of probing native and nonnatural DNA. The nucleophilic addition of aryl Grignard reagents to either a protected 2'-deoxy-1'-chloro-ribofuranose or a protected 2'-deoxy-ribonolactone was the key synthetic step and afforded C-nucleosides in good yields. Both routes resulted in a final product that was >/=90% of the beta-anomer. Amide- and ether-based linkers for attachment of trans-stilbene to the nucleobase were assessed for utility during synthesis and in binding of the ligands to a blue-fluorescent monoclonal antibody. X-ray structures of each complex were obtained and serve as a guideline for second-generation stilbene-tethered C-nucleosides. The development of these hydrophobic nucleosides will be useful in current native and nonnatural DNA studies and invaluable for investigations regarding novel, nonnatural genomes in the future.
Department of Chemistry, The Scripps Research Institute and the Skaggs Institute for Chemical Biology, 10550 N. Torrey Pines Road, La Jolla, CA 92037, USA.
D W
DW
Chen
A E
AE
Beuscher
R C
RC
Stevens
P
P
Wirsching
R A
RA
Lerner
K D
KD
Janda
D000906:Antibodies / Q000737:chemistry*; D018360:Crystallography, X-Ray; D005453:Fluorescence; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D009705:Nucleosides / Q000138:chemical synthesis*; D013267:Stilbenes / Q000737:chemistry*
D000906:Antibodies; D009705:Nucleosides; D013267:Stilbenes