- A cell-penetrating artificial metalloenzyme regulates a gene switch in a designer mammalian cell
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Complementing enzymes in their native environment with either homogeneous or heterogeneous catalysts is challenging due to the sea of functionalities present within a cell. To supplement these efforts, artificial metalloenzymes are drawing attention as they combine attractive features of both homogeneous catalysts and enzymes. Herein we show that such hybrid catalysts consisting of a metal cofactor, a cell-penetrating module, and a protein scaffold are taken up into HEK-293T cells where they catalyze the uncaging of a hormone. This bioorthogonal reaction causes the upregulation of a gene circuit, which in turn leads to the expression of a nanoluc-luciferase. Relying on the biotin-streptavidin technology, variation of the biotinylated ruthenium complex: the biotinylated cell-penetrating poly(disulfide) ratio can be combined with point mutations on streptavidin to optimize the catalytic uncaging of an allyl-carbamate-protected thyroid hormone triiodothyronine. These results demonstrate that artificial metalloenzymes offer highly modular tools to perform bioorthogonal catalysis in live HEK cells.
- Okamoto, Yasunori,Kojima, Ryosuke,Schwizer, Fabian,Bartolami, Eline,Heinisch, Tillmann,Matile, Stefan,Fussenegger, Martin,Ward, Thomas R.
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- IMMUNOTHERAPY AGAINST SEVERAL TUMORS, SUCH AS LUNG CANCER, INCLUDING NSCLC
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The present invention relates to peptides, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated cytotoxic T cell (CTL) peptide epitopes, alone or in combination with other tumor-associated peptides that serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses. The present invention relates to more than 70 novel peptide sequences and their variants derived from HLA class I and HLA class II molecules of human tumor cells that can be used in vaccine compositions for eliciting anti-tumor immune responses.
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- 3, 5-diiodo-O-[ 3-phenyl]-production of sulfate derivative of L-thyrosine (by machine translation)
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The present invention relates to a process for the preparation of the mono sodium salt of the derivative 3,5-diiodo-O-[3-iodo-4-(sulphooxy)phenyl]-L- tyrosine (T3S) by starting from the corresponding phenolic compound, in the presence of chlorosulfonic acid and dimethylacetamide as a solvent. The so obtained T3S compound may conveniently be isolated in a pure form as a solid in good yields. The present invention further relates to the process for T3S preparation, wherein the starting reagent is T2 and further comprising the formulation of such compound in tablets. Furthermore, the invention discloses non-radioactive immunoassays based on T3S derivatives.
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Paragraph 0060
(2017/01/05)
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- Process development and scale-up of T3-Sulfate, a new prodrug alternative to the conventional hormone therapy of hypothyroidism
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An efficient and scalable preparation of the thyroid hormone analogue O-[3-iodo-4-(sulfooxy)phenyl]-3,5-diiodo-L-tyrosine sodium salt (T3-sulfate, 1) is reported. The synthesis involved monoiodination of O-(4-hydroxyphenyl)-3,5-diiodo- L-tyrosineto give liothyronine (2) which was sulfated with chlorosulfonic acid in N,N -dimethylacetamide. Crude T3-sulfate was initially purified by chromatography on polystyrene resin Amberlite XAD 1600 and then crystallized with ethanol. This strategy was scaled-up to give a process suitable for the production of kilogram quantities of API, needed to support preclinical and clinical studies.
- Lattuada, Luciano,Argese, Maria,Boi, Valeria,Galimberti, Laura,Gazzetto, Sonia
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p. 1175 - 1180
(2014/12/10)
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- A concise synthesis of thyroxine (T4) and 3,5,3'-Triiodo-L-thyronine (T3)
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The mono- and di-iodo derivatives of 1-oxaspiro[2,5]bicycloocta-4,7-dien-6-one, 8 and 9, reacted readily with 3,5-diiodo-L-tyrosine at pH 8.0 to give 3,5,3'-triiodo-L-thyronine (T3) and thyroxine in 70% and 94% yields respectively. In turn, 8 and 9 were prepared by the sodium bismuthate oxidation of their corresponding iodinated p-hydroxybenzyl alcohol derivatives, 6 and 7 in 32% and 37% yields.
- Salamonczyk, Grzegorz M.,Oza, Vibha B.,Sih, Charles J.
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p. 6965 - 6968
(2007/10/03)
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