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AssigneeMedical Research Council
InventorsDario Alessi, Ricardo Biondi, David Komander
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A liquid reactant metal alloy (210) includes at least one chemically active metal for reacting with non-radioactive material in a mixed waste stream being treated. The reactant alloy (210) also includes at least one radiation absorbing metal. Radioactive isotopes in the waste stream alloy with, or disperse in, the chemically active and radiation absorbing metals such that the radiation absorbing metals are able to absorb a significant portion of the radioactive emissions associated with the isotopes. Non-radioactive constituents in the waste material are broken down into harmless and useful constituents, leaving the alloyed radioactive isotopes in the liquid reactant alloy. The reactant alloy may then be cooled to form one or more ingots in which the radioactive isotopes are effectively isolated and surrounded by the radiation absorbing metals. These ingots comprise storage products for the radioactive isotopes. The ingots may be encapsulated in one or more layers of radiation absorbing material and then stored.
A method for selecting or designing a compound for modulating the activity of phosphoinositide dependent protein kinase 1 (PDK1), the method comprising the step of using molecular modelling means to select or design a compound that is predicted to interact with the protein kinase catalytic domain of PDK1, wherein a three-dimensional structure of at least a part of the protein kinase catalytic domain of PDK1 is compared with a three-dimensional structure of a compound, and a compound that is predicted to interact with the said protein kinase catalytic domain is selected, wherein the three-dimensional structure of at least a part of the protein kinase catalytic domain of PDK1 is a three-dimensional structure (or part thereof) determined for a polypeptide consisting of residues equivalent to residues 51 to 359 of full length human PDK1, or a fragment or fusion thereof.
A method for selecting or designing a compound for modulating the activity of a hydrophobic pocket (PIF binding pocket)-containing protein kinase having a hydrophobic pocket in the position equivalent to the hydrophobic pocket of human PDK1 that is defined by residues including Lys115, Ile118, Ile119, Val124, Val127 and/or Leu155 of full-length human PDK1 and further having a phosphate binding pocket in the position equivalent to the phosphate binding pocket of human PDK1 that is defined by residues including Lys76, Arg131, Thr148 and/or Gln150, the method comprising the step of using molecular modelling means to select or design a compound that is predicted to interact with the said hydrophobic pocket-containing protein kinase, wherein a three-dimensional structure of a compound is compared with a three-dimensional structure of the said phosphate binding pocket and optionally also the hydrophobic pocket and/or αC helix or region interacting therewith, and a compound that is predicted to interact with the said phosphate binding pocket and optionally also the hydrophobic pocket and/or αC helix or region interacting therewith, is selected.
A method for assessing the activation state of a structure for a protein kinase, wherein the structure is analysed using principle component analysis of the structure co-ordinates.
A mutated protein kinase, wherein the protein kinase before mutation has a hydrophobic pocket in the position equivalent to the hydrophobic pocket (PIF-binding pocket) of human PDK1 that is defined by residues including Lys115, Ile118, Ile119, Val124, Val127 and/or Leu155 of full-length human PDK1 and further has a phosphate binding pocket in the position equivalent to the phosphate binding pocket of human PDK1 that is defined by residues including Lys76, Arg131, Thr148 and/or Gln150, and wherein one or more residues equivalent to Ile118, Val124, Val127, Lys76 or Thr148 forming part of the hydrophobic pocket or phosphate binding pocket of the protein kinase is mutated.
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A crystalline form of a polypeptide consisting of residues 51 to 359 of full length human PDK1 or a fusion thereof.
Dependencies are inferred from the claim text.