Proteins containing a C-terminal thioester are important intermediates in semi-synthesis. Currently there is one main method for the synthesis of protein thioesters that relies upon the use of engineered inteins. The invention involves, in some aspects a method, utilizing Sortase A, for preparation of recombinant proteins containing a C-terminal .sup.αthioester. This new method for double ligatation is useful for synthesizing new or naturally occurring molecules such as a protein thioester.

The present invention relates to an inhibitor of necroptosis for use in preventing the metastasis of tumours. Further, the present invention relates to a method of preventing the metastasis of tumours by inhibiting necroptosis and to a method for modulating the transmigration of metastasising tumour cells through endothelium by modulating necroptosis as well as to an in-vitro method of identifying an inhibitor of necroptosis suitable as a lead compound and/or as a medicament for the prevention of tumour metastasis. Moreover, the present invention also relates to a method of identifying necroptotic and necrotic cells.

The present invention relates to an inhibitor of necroptosis for use in preventing the metastasis of tumours. Further, the present invention relates to a method of preventing the metastasis of tumours by inhibiting necroptosis and to a method for modulating the transmigration of metastasising tumour cells through endothelium by modulating necroptosis as well as to an in-vitro method of identifying an inhibitor of necroptosis suitable as a lead compound and/or as a medicament for the prevention of tumour metastasis. Moreover, the present invention also relates to a method of identifying necroptotic and necrotic cells.

1,3-Dipole-functional compounds (e.g., azide functional compounds) can be reacted with certain alkynes in a cyclization reaction to form heterocyclic compounds. Useful alkynes (e.g., strained, cyclic alkynes) and methods of making such alkynes are also disclosed. The reaction of 1,3-dipole-functional compounds with alkynes can be used for a wide variety of applications including the immobilization of biomolecules on a substrate.

1,3-Dipole-functional compounds (e.g., azide functional compounds) can be reacted with certain alkynes in a cyclization reaction to form heterocyclic compounds. Useful alkynes (e.g., strained, cyclic alkynes) and methods of making such alkynes are also disclosed. The reaction of 1,3-dipole-functional compounds with alkynes can be used for a wide variety of applications including the immobilization of biomolecules on a substrate.

The invention describes a method and compounds for the prevention and treatment of infections with intracellular organisms, the treatment of tumors, and the prevention of infectious and allergic diseases by vaccination.

The invention describes a method and compounds for the prevention and treatment of infections with intracellular organisms, the treatment of tumors, and the prevention of infectious and allergic diseases by vaccination.

This invention relates to a method of inhibiting neuronal cell death, including protecting neuronal cells from cell death and the effects of stress, such as high or low pH, comprising administering to the cells an effective amount of Teneurin C-terminal Associated Peptide (TCAP). The invention provides the use of TCAP to prevent and/or treat a number of brain conditions, such as hypoxia-ischemia and brain alkalosis or various brain or spinal cord injuries due to physical or physiological stresses. In one aspect the invention provides a use of TCAP to increase β-tubulin, β-actin levels in neuronal cells and/or to increase fasciculation among neuronal cells, in culture or in tissue. In another aspect, the invention provides a method of treating various pH induced neuronal conditions.

This invention relates to a method of inhibiting neuronal cell death, including protecting neuronal cells from cell death and the effects of stress, such as high or low pH, comprising administering to the cells an effective amount of Teneurin C-terminal Associated Peptide (TCAP). The invention provides the use of TCAP to prevent and/or treat a number of brain conditions, such as hypoxia-ischemia and brain alkalosis or various brain or spinal cord injuries due to physical or physiological stresses. In one aspect the invention provides a use of TCAP to increase β-tubulin, β-actin levels in neuronal cells and/or to increase fasciculation among neuronal cells, in culture or in tissue. In another aspect, the invention provides a method of treating various pH induced neuronal conditions.

A method for producing a ribosome display complex includes obtaining a ribosome complex including an unmodified polypeptide chain, an mRNA molecule and a ribosome by initiating translation of the mRNA molecule in a cell-free peptide synthesis system including the ribosome, and modifying the unmodified polypeptide chain by reacting a side chain reactive functional group in the unmodified polypeptide chain with a modifying reagent to produce a ribosome display complex including a modified polypeptide chain, the mRNA molecule and the ribosome. The unmodified polypeptide chain includes at least one reactive amino acid residue selected from the group consisting of a cysteine residue, a lysine residue, a histidine residue and a tryptophan residue. The at least one reactive amino acid residue includes the side chain reactive functional group, and the mRNA molecule includes a base sequence encoding an amino acid sequence of the polypeptide chain.