A Drug Discovery Platform Using Novel Labeled Uridine Analogs: Unique moieties contribute to molecular biology research
Summary Background: Uracil is a nucleic acid base that, when bound to ribose or deoxyribose, forms uridine or deoxyuridine, respectively. Certain analogs of uridine and deoxyuridine have been synthesized and used in a variety of applications. For example, deoxyribouridine analogs containing a 5-amino group have been prepared and used as anticancer, antiviral, and antibacterial agents. In other cases, 5-amino deoxyribouridine analogs have been made with fluorescent compounds for use in DNA sequencing and microarray technology. This success has led scientist to search for new 5-amino deoxyribouridine analogs as well as platforms for their use.
Invention: Novel 5-amino deoxyribouridine analogs. The analogs are labeled with a radioactive or fluorescent moiety and incorporated into nucleic acid by PCR for use in genomic research applications. One assay design involves a fluorescent 5-amino deoxyribouridine DNA analog as a target for the discovery of DNA binding agents. The DNA binding agents (peptides, proteins, small molecules) represent lead anticancer, antiviral, and antibacterial therapies.
Applications Advantages: Fluorescently labeled 5-amino-2'-deoxyuridine analogs, in contrast to a natural 2'-deoxyuridine nucleotides are excellent substrates for base specific cleavage with oxidizing agents. The use of oxidizing agents to cleave uracil bases in a labeled nucleic acid is a tool to identify the specificity of the DNA binding agents. The simple and efficient mechanism of 5-amino-2'-deoxyuridine synthesis generates 95% yield and is cost-effective.
Commercial Applications: A drug discovery platform for anticancer, antiviral, and antibacterial therapies in academic and industrial research laboratories. The labeled analogs can also be used in microarray and nucleic acid sequencing applications.
Market: Genomic research
Publication: Storek, M. J.; Suciu, A.; Verdine, G. L."5-Amino-2'-Deoxyuridine, a Novel Thymidine Analogue for High- Resolution Footprinting of Protein-DNA Complexes," Org. Lett.2002, 4, 3867-3869.
Storek, M. J.; Ernst, A.; Verdine, G. L. "High-resolution footprinting of sequence-specific protein-DNA contacts," Nature Biotechnology 2002, 20, 183-186
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Verdine, Gregory L
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