HTLV PROTEASE · synthesis and inhibition
6РП — Действия „Мария Кюри“
- Период
- 2007-03-01 → 2009-02-28
- Финансиране от ЕС
- 80 000 €
- Участници
- 1
- Схема
- EIF
Линиите свързват координатора с партньорите.
Накратко на български
Протеазата на HTLV вируса се синтезира химически, за да се създадат нейни естествени и изкуствени варианти, включително огледален образ на протеина. Това помага за разработването на по-стабилни инхибитори и прилагането на метода при други протеини.
Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.
Резултати накратко
Final Activity Report Summary - HTLV PROTEASE (HTLV Protease: Synthesis and Inhibition)
Our work in this project led to the development of a new method for the chemical synthesis of protein. Chemical synthesis of protein allows the full control on the chemical structure of proteins, which could lead to product with new physical and chemical properties. This is in contrary to the biological methods where it is limited to certain building blocks that are used to assemble the protein structure. Our new methodology will allow us to synthesise the HTLV protease in its natural form as well as its unnatural variations so one may perform studies and achieve results that are otherwise cannot be obtained. For example, we are making progress of making the mirror image of this protein to achieve inhibitors that are have higher stability in biological system. Together, our results will lead to the chemical synthesis of other proteins as well as to the development of new HTLV protease inhibitors.
Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз
Цел на проекта
Human T-cell leukemia virus type 1 (HTLV-I), the first human retrovirus to be discovered, has been shown to be clinically associated with adult T-cell leukemia/lymphoma and tropical spastic paresis/HTLV-I-associated myelopathy. Currently, it is estimated that 15 million to 20 million individuals worldwide are infected with HTLV-I, for which there is no effective treatment, as is the case for adult T-cell leukemia. For the virus to mature and assemble infectious particles, the polyproteins must be processed by retroviral protease. HTLV aspartic protease is thus considered an attractive target for the development of inhibitors to treat HTLV-I infections.However, to date only very few peptide-based inhibitors against HTLV-I protease have been reported. The development of effective inhibitors against HTLV-I protease is thus the major goal of this proposal. The first step will be to synthesize by means of native chemical ligation (NCL)" HTLV-I protease, which is a small dimmer comprising two identical subunits, each containing 125 amino acids. NCL is particularly suitable for the synthesis of large quantities of proteins for biological studies. There will thus be sufficient quantities of material available for the screening process to discover HTLV-I protease inhibitors.The NCL strategy will also be used to prepare proteases with unnatural modifications, which will be used for inhibition studies. New ligation chemistries will also be explored for the synthesis of polypeptides from free cysteine peptides. It is believed that the proposed study will lead to the development of novel inhibitors against HTLV protease, which will, in turn, inspire the synthesis of similar inhibitors against other aspartic proteases involved in a variety of diseases. It is hoped that the tools developed for the chemical synthesis of HTLV-I protease will further enhance our ability to chemically synthesize other targets, leading to an understanding of protein function and enzyme activity."
Оригинален текст от CORDIS (на английски).
Участници
- BEN GURION UNIVERSITY OF THE NEGEV · BEER-SHEVAКоординаторИзраел
Връзки
Данни: CORDIS, © Европейски съюз