摘要:
The present invention relates to in silico methods for identifying compounds which decrease or prevent the binding of the viral RNA-dependent RNA polymerase from the Orthomyxoviridae family or variant thereof, to its ligand, (preferably to cellular Pol II, more preferably to CTD), as well as methods of producing the identified compounds. The present invention also relates to a compounds identifiable and/or producible by said methods. The present invention also relates to antibodies directed against the binding site of the RNA-dependent RNA polymerase, to its ligand (in particular to cellular Pol II, in particular to CTD of Pol II) as well as nucleic acids encoding said antibodies and vectors comprising the nucleic acid. The present invention relates to a pharmaceutical composition producible according to said method, and/or comprising said compound, said antibody, said nucleic acid, or said vector. The present invention also relates to the use of said compound, said antibody, said nucleic acid, said vector or said pharmaceutical in treating, ameliorating, or preventing disease conditions caused by viral infections with viruses of the Orthomyxoviridae family.
摘要:
The present invention is directed to methods and compositions for TnpI-mediated genetic engineering using the Bacillus thurungiensis recombinase TnpI and the TnpI recombination substrates TRT or TRT', and variants thereof. In particular, the invention relates to TRT or TRT' sequences, and variants thereof, vectors, cells and kits useful for TnpI-mediated genetic recombination, as well as methods for the use of TRT or TRT' sequences for TnpI-mediated genetic engineering.
摘要:
The present invention provides novel compounds that inhibit cell proliferation, in particular through the disruption of chromosome segregation and uses of these compounds for treating, ameliorating or preventing diseases, conditions or disorders benefiting from the antiproliferative consequences of the disruption of chromosome segregation, in particular hyperproliferative diseases.
摘要:
A method of deducing the sequence of a protein by analysing tandem mass spectrometry data. The protein is subjected to partial isotopic labelling by enzymatic digestion in a water mixture comprising a non-natural abundance of H 2 1s O. Differential scanning mass spectrometry is applied to the peptide fragments obtained from the digestion. Peaks in the spectra are analyzed to ascertain whether they arise from isotopically labeled fragments or not. A filtered spectrum is calculated that just comprises peaks from the y-ions. The sequence of the peptide is deduced by computing the difference in the mass between adjacent y-ion peaks.
摘要:
The present invention relates to a new nucleic acid construct capable of binding to the PB1 RNA synthesis active site of influenza polymerase. The nucleic acid construct allows capturing the structure of the transcription initiation state of influenza polymerase. The present invention further pertains to methods for obtaining images or crystallography data on an influenza polymerase in a functional or active state, methods for identifying, selecting or designing a compound which inhibits influenza RNA polymerase, and to such compounds per se. Further provided are pharmaceutical compositions comprising such compounds and the compounds or pharmaceutical compositions for use in treating, ameliorating, or preventing a disease caused by viral infections with negative-sense single stranded RNA viruses.
摘要:
The present invention describes methods for determining the risk that a breast precursor lesion will progress to invasive breast cancer and/or the risk of recurrent non-invasive disease in a patient, comprising detecting the presence and/or level of PAPPA and/or PAPPA functional activity in a breast tissue sample obtained from the patient, wherein if PAPPA is not present, or is present at a reduced amount compared to a control, there is the risk of progression to invasive cancer and/or the risk or recurrent disease. In an alternative embodiment, the diagnosis can be carried out by identifying the proportion of mitotic cells in a patient sample that are in prophase or pro- metaphase, wherein if the proportion of cells in prophase or pro-metaphase is 30% or more,this indicates a risk of progression to invasive breast cancer and/or risk of recurrent disease. The present invention also enables the chemosensitisation of mitotically delayed breast cancer cells to anti-proliferative agents, preferably anti-mitotic agents, by restoring normal progression through mitosis. In this embodiment a first drug is applied to release breast cancer cells from the mitotic block and, sequentially,a second drug affecting proliferating cells is administered for cancer cell killing.
摘要:
The present invention relates to the field of microfluidics and in particular to devices and methods for sorting objects in microfluidic channels. These devices and methods allow for fast and robust sorting in two-way and multi-way setups. They also enable sorting over extended periods of time.
摘要:
The present invention relates to new adenoviral coat protein based delivery vehicles. They are based on a modified penton base protomers that assemble into VLPs. Exposed areas of the penton base proteins can be modified to allow the VLP to specifically bind to any target and/or to comprise any desired peptide epitope. Additional cargo, e.g. drugs, proteins, or nucleic acids, can reversibly or irreversibly attached to the VLP via engineered fibre protein fragments. The present invention relates to such engineered penton base protomers, engineered proteins comprising an adenovirus fibre protein N-terminal fragment specifically binding to an adenovirus fibre protein binding cleft of a penton base protomer, VLPs comprising the engineered penton base protomers and optionally engineered proteins comprising an adenovirus fibre protein N-terminal fragment specifically binding to an adenovirus fibre protein binding cleft of a penton base protomer, nucleic encoding the engineered proteins, the VLPs as well as methods of producing the proteins and VLPs.