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.
Chen
D W
DW
Department of Chemistry, The Scripps Research Institute and the Skaggs Institute for Chemical Biology, 10550 N. Torrey Pines Road, La Jolla, CA 92037, USA.
Beuscher
A E
AE
Stevens
R C
RC
Wirsching
P
P
Lerner
R A
RA
Janda
K D
KD
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