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A drug discovery platform using novel labeled uridine analogs contribute to molecular biology research



Technology:
Novel 5-amino deoxyribouridine analogs

Markets Addressed


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.

As for commercial applications, it can be used as a drug discovery platform in genomic research 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.

Innovations and Advantages


This invention consists of 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.

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.

Additional Information


Intellectual Property Status: Patent pending

Publications:
-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



Inventor(s):
    Storek, Michael J.
    Verdine, Gregory L.

Categories:
For further information, please contact:
Vivian Berlin, Director of Business Development
(617) 496-0474
Reference Harvard Case #1823