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November 12, 2008, Lincoln, NE: Protease substrates provide a sensitive method to detect protease activity, measure potency of inhibitors and screen compound collections for discovery of drug candidates. LI-COR Biosciences now offers three different IRDye NIR-FRET Protease Substrates: IRDye 800CW/QC-1 HIV-1, IRDye 800CW/QC-1 BACE, and IRDye 800CW/QC-1 CSP-3.
"These substrates have low intrinsic fluorescence due to self-quenching of the conjugated dye by our novel IRDye QC-1 quencher," says Jim Wiley, LI-COR strategic marketing manager. "These new substrates can be used for the highly sensitive detection of protease activity via near-infrared fluorescence detection on the Odyssey® Infrared Imaging System, Aerius® Automated Imaging System, or other imaging systems with near infrared detection capabilities." "NIR detection dramatically reduces background, scattering and interference from other compounds," says Wiley. He notes that all three substrates have excellent water solubility.
HIV-1 protease performs an essential step in the life cycle of HIV virus by cleaving Gag and Gas-Pol polyproteins into the constituent proteins that make up infectious virus particles. Anti-AIDS drugs targeting HIV-1 protease substantially suppress HIV viral replication and dramatically reduce mortality among HIV infected patients.
Beta-Secretase (BACE-1) has been identified as a key enzyme that mediates a critical step in the formation of β-amyloid (Aβ40/42) by acting upon the β-amyloid precursor protein (β-APP). Deposits of β-amyloid form plaques in the brain that lead to damage and death of nerve cells. Plaques are one of the abnormal structures that are characteristic of Alzheimer's disease. Since the discovery of the function of Beta-Secretase, it has been established as a validated therapeutic target for Alzheimer's disease.
Caspases are a family of intracellular cysteine proteases that are vital in the process of apoptosis (programmed cell death). Caspase-3 functions as the most downstream executioner in the caspase-apoptosis signaling cascade. Activation of Caspase-3 by upstream initiator caspases (Caspases 2, 8, 9) results in the final execution of cell death. Insufficient or accelerated apoptosis is implicated in a variety of diseases such as cancer, immune system diseases and nervous system disease.
LI-COR Biosciences is a leading manufacturer of near-infrared imaging platforms, analysis software, and LI-COR IRDye Infrared Dye reagents for genomic, proteomic, and molecular imaging applications. LI-COR pioneered the development of near-infrared fluorescence detection systems for DNA sequencing and today provides systems for drug discovery, protein research, small animal imaging, and undergraduate training. LI-COR instruments for photosynthesis, carbon dioxide analysis and light measurement are recognized worldwide for standard-setting innovation in plant science research and environmental monitoring. Founded in 1971, the privately held company is based in Lincoln, Nebraska, with subsidiaries in Germany and the United Kingdom. LI-COR systems are used in over 100 countries and are supported by a global network of distributors.