Abstract: The present invention provides methods for the non-enzymatic cleavage of target nucleic acids, for example for use in epigenomic and epitranscriptomic mapping and therapy. The method comprises contacting a target nucleic acid molecule with a bifunctional probe comprising a cleavage group and a covalent binding group such that the bifunctional probe covalently binds to the target nucleic acid molecule and cleaves the 5 target nucleic acid molecule bound thereto. Also provided is a method of selectively cleaving a target nucleic acid in a cell, a method for determining the modification of nucleic acid molecules by a nucleic acid modification enzyme in a cell, and a bifunctional probe for use in the methods.

Abstract: This invention relates to the finding that Piperlongumine compounds, such as Piperlongumine and analogues, derivatives and prodrugs thereof, are reversible, allosteric antagonists of transient receptor potential vanilloid 2 channel (TRPV2).

Abstract: This invention relates to the finding that Piperlongumine compounds, such as Piperlongumine and analogues, derivatives and prodrugs thereof, are reversible, allosteric antagonists of transient receptor potential vanilloid 2 channel (TRPV2). Methods of treatment of conditions that are characterised by TRPV2 expression using Piperlongumine compounds and Piperlongumine compounds for use in such treatments are provided.

Abstract: This invention relates to the treatment of conditions, such as cancer, associated with 5-lipoxygenase (5-LO) expression using ?-lapachone compounds that inhibit 5-lipoxygenase (5-LO), such as ?-lapachone and derivatives thereof. Methods of treatment of conditions associated with 5-lipoxygenase (5-LO) expression as well as medical uses of ?-lapachone compounds in such methods are provided, as well as methods of selecting or prognosing cancer patients.

Abstract: This invention relates to the finding that the inhibition of solute carrier family 6 member 2 (Slc6a2) exert a sympathomimetic effect outside the brain that promotes weight loss without concomitant hypophagia or hyperkinesia. Compounds for the inhibition of Slc6a2 outside the brain, as well as methods of promoting weight loss and treating obesity using such compounds are provided.

Abstract: This invention relates to the finding that Piperlongumine compounds, such as Piperlongumine and analogues, derivatives and prodrugs thereof, are reversible, allosteric antagonists of transient receptor potential vanilloid 2 channel (TRPV2).

Abstract: The invention relates to methods for selectively converting a cysteine residue in a peptide or protein to the dehydroalanine (Dha) residue. The method also works on selenocysteine and substituted cysteine and selenocysteine residues, resulting in the Dha residue which may be converted to any natural or unnatural amino acid residue desired without the alteration of the remainder of the peptide or protein. The invention also allows ligation of a desired peptide at any point rather than at a point where there should be a naturally occurring cysteine, thereby allowing native chemical ligation to be used in the synthesis of peptides that do not contain cysteine. The methodology allows for the synthesis of very large peptides.

Abstract: The invention relates to methods for selectively converting a cysteine residue in a peptide or protein to the dehydroalanine (Dha) residue. The method also works on selenocysteine and substituted cysteine and selenocysteine residues, resulting in the Dha residue which may be converted to any natural or unnatural amino acid residue desired without the alteration of the remainder of the peptide or protein. The invention also allows ligation of a desired peptide at any point rather than at a point where there should be a naturally occurring cysteine, thereby allowing native chemical ligation to be used in the synthesis of peptides that do not contain cysteine. The methodology allows for the synthesis of very large peptides.

Abstract: The invention relates to methods for selectively converting a cysteine residue in a peptide or protein to the dehydroalanine (Dha) residue. The method also works on selenocysteine and substituted cysteine and selenocysteine residues, resulting in the Dha residue which may be converted to any natural or unnatural amino acid residue desired without the alteration of the remainder of the peptide or protein. The invention also allows ligation of a desired peptide at any point rather than at a point where there should be a naturally occurring cysteine, thereby allowing native chemical ligation to be used in the synthesis of peptides that do not contain cysteine. The methodology allows for the synthesis of very large peptides.