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Novel method could improve the performance of proteins used therapeutically
Date:3/9/2011

FINDINGS: Whitehead Institute scientists have created a method that uses the enzyme sortase A to site-specifically modify proteins. Using this technique, researchers were able to increase potency, slow the metabolism, and improve thermal stability of several proteins, including interferon alpha 2 (IFN-alpha 2) and granulocyte colony-stimulating factor 3 (GCSF-3). IFN-alpha 2 is used to treat a variety of diseases, including leukemia, melanoma, and chronic hepatitis C, while GCSF-3 (known as filgrastim and marketed as Neupogen) is administered to patients with neutropenia.

RELEVANCE: Sortase could be used to improve other proteins used as therapeutics, for example those with IFN-alpha 2's characteristic four-helix bundle structure. Such proteins include erythropoietin (EPO), interleukin (IL) 2 (known as aldesleukin and marketed as Proleukin), IL-4, IL-7, IL9-, and IL-15. This same strategy could likely be applied to other therapeutically important proteins, but with a different folding pattern, as well.

Novel method could improve the performance of proteins used therapeutically

CAMBRIDGE, Mass. (March 9, 2011) Whitehead Institute scientists have created a method that site-specifically modifies proteins to exert control over their properties when administered therapeutically. The technique should be useful to increase potency, slow metabolism, and improve thermal stability of therapeutically useful proteins, such as interferon alpha 2 (IFN-alpha 2), which is used to treat variety of diseases, including leukemia, melanoma, and chronic hepatitis C.

The method, reported this month in Proceedings of the National Academy of Sciences (PNAS), uses the enzyme sortase A and can be applied to tailor proteins that possess a structure found in IFN-alpha 2, referred to as a four-helix bundle. Such proteins include erythropoietin (EPO), granulocyte colony-stimulating factor 3 (GCSF-3, known as filgrastim and marketed as Neupog
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Contact: Nicole Giese
giese@wi.mit.edu
617-258-6851
Whitehead Institute for Biomedical Research
Source:Eurekalert

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