Abstract: The present invention relates to series of peptidomimetic compounds selectively targeting CBX8 of polycomb chromobox protein homolog proteins. Pharmaceutical compositions of those compounds and methods of using them in the treatment of diseases involved CBX8 pharmacology, including various cancers and leukemia, by administering therapeutically effective amounts of such compound alone or together with other therapeutics, are within the scope of this disclosure.

Abstract: The present invention relates to series of peptidomimetic compounds selectively targeting CBX8 of polycomb chromobox protein homolog proteins. Pharmaceutical compositions of those compounds and methods of using them in the treatment of diseases involved CBX8 pharmacology, including various cancers and leukemia, by administering therapeutically effective amounts of such compound alone or together with other therapeutics, are within the scope of this disclosure.

Abstract: The present application relates to an assay method using affinity crosslinking of DNA-linked ligands to proteins to enable small molecule screening and determination of apparent affinity constants of ligands to the proteins. This method has been applied to determine 96 compounds' dissociation constants to a protein target simultaneously, and directly determine a compound's IC50 against five protein targets concurrently in crude cell lysates. Additionally, this approach was used to screen a Library of Pharmacologically Active Compounds (LOPAC) library against dihydrofolate reductase (eDHFR), enabling the discovery of a novel eDHFR inhibitor (IC50=7.9 ?M). An assay kit and the method of uses are within the scope of this disclosure.

Abstract: The present invention relates to series of peptidomimetic compounds selectively targeting CBX8 of polycomb chromobox protein homolog proteins. Pharmaceutical compositions of those compounds and methods of using them in the treatment of diseases involved CBX8 pharmacology, including various cancers and leukemia, by administering therapeutically effective amounts of such compound alone or together with other therapeutics, are within the scope of this disclosure.

Abstract: Systems, kits, and methods for detecting and quantifying proteomic activity using DNA-encoded probes are provided, where the proteomic activity may be enzymatic activity or ligand binding affinity. Such systems and methods encode quantitative proteomic activity information into DNA sequence populations and utilize DNA-linked substrates or ligands as activity probes. The systems, kits, and methods that are directed to detecting ligand affinity further include crosslinking steps to ensure the integrity of the DNA-linked ligands during purification and washing. Signal detection involves the chemical manipulation of a probe population downstream of sample exposure and application of purifying, selective pressure for desired products. Selection-induced changes in DNA abundance between the initial pool and the purified pool indicate sample activity.

Abstract: Systems, kits, and methods for detecting and quantifying proteomic activity using DNA-encoded probes are provided, where the proteomic activity may be enzymatic activity or ligand binding affinity. Such systems and methods encode quantitative proteomic activity information into DNA sequence populations and utilize DNA-linked substrates or ligands as activity probes. The systems, kits, and methods that are directed to detecting ligand affinity further include crosslinking steps to ensure the integrity of the DNA-linked ligands during purification and washing. Signal detection involves the chemical manipulation of a probe population downstream of sample exposure and application of purifying, selective pressure for desired products. Selection-induced changes in DNA abundance between the initial pool and the purified pool indicate sample activity.

Abstract: The present invention relates to series of peptidomimetic compounds selectively targeting CBX8 of polycomb chromobox protein homolog proteins. Pharmaceutical compositions of those compounds and methods of using them in the treatment of diseases involved CBX8 pharmacology, including various cancers and leukemia, by administering therapeutically effective amounts of such compound alone or together with other therapeutics, are within the scope of this disclosure.

Abstract: Systems, kits, and methods for detecting and quantifying proteomic activity using DNA-encoded probes are provided, where the proteomic activity may be enzymatic activity or ligand binding affinity. Such systems and methods encode quantitative proteomic activity information into DNA sequence populations and utilize DNA-linked substrates or ligands as activity probes. The systems, kits, and methods that are directed to detecting ligand affinity further include crosslinking steps to ensure the integrity of the DNA-linked ligands during purification and washing. Signal detection involves the chemical manipulation of a probe population downstream of sample exposure and application of purifying, selective pressure for desired products. Selection-induced changes in DNA abundance between the initial pool and the purified pool indicate sample activity.

Abstract: The present invention provides methods for enhancing the fragmentation of peptides for mass spectrometry by modifying the peptides with a tagging reagent containing a functional group, such as a tertiary amine, having a greater gas-phase basicity than the amide backbone of the peptide. These high gas-phase basicity functional groups are attached to a peptide by reacting the tagging reagent to one or more available carboxylic acid groups of the peptide. Linking these high gas-phase functional groups to the peptides leads to higher charge state ions from electrospray ionization mass spectrometry (ESI-MS), which fragment more extensively during fragmentation techniques, particularly non-ergodic fragmentation techniques such as electron capture dissociation (ECD) and electron transfer dissociation (ETD).

Abstract: Relative quantification of metabolites by Electrospray Ionization Mass Spectrometry (ESI-MS) requiring a mechanism for simultaneous analysis of multiple analytes in two or more samples. Labeling reagents that are reactive to particular compound classes and differ only in their isotopic compositions facilitate relative quantification. Heavy and light isotopic forms of methylacetimidate were synthesized and used as labeling reagents for quantification of amine-containing molecules. Heavy and light isotopic forms of formaldehyde and cholamine were also synthesized and used independently as labeling reagents for quantification of amine-containing and carboxylic acid-containing molecules, such as found in biological samples. The labeled end-products are positively charged under normal acidic conditions involving conventional Liquid Chromatography Mass Spectrometry (LC/MS) applications.

Abstract: Relative quantification of metabolites by Electrospray Ionization Mass Spectrometry (ESI-MS) requiring a mechanism for simultaneous analysis of multiple analytes in two or more samples. Labeling reagents that are reactive to particular compound classes and differ only in their isotopic compositions facilitate relative quantification. Heavy and light isotopic forms of methylacetimidate were synthesized and used as labeling reagents for quantification of amine-containing molecules. Heavy and light isotopic forms of formaldehyde and cholamine were also synthesized and used independently as labeling reagents for quantification of amine-containing and carboxylic acid-containing molecules, such as found in biological samples. The labeled end-products are positively charged under normal acidic conditions involving conventional Liquid Chromatography Mass Spectrometry (LC/MS) applications.

Abstract: Relative quantification of metabolites by Electrospray Ionization Mass Spectrometry (ESI-MS) requiring a mechanism for simultaneous analysis of multiple analytes in two or more samples. Labeling reagents that are reactive to particular compound classes and differ only in their isotopic kit facilitating relative quantification and providing tangible evidence for the existence of specific functional groups. Heavy and light isotopic forms of methylacetimidate were synthesized and used as labeling reagents for quantification of amine-containing molecules, such as biological samples. Heavy and light isotopic forms of formaldehyde and cholamine were also synthesized and used independently as labeling reagents for quantification of amine-containing and carboxylic acid-containing molecules, such as found in biological samples. Advantageously, the labeled end-products are positively charged under normal acidic conditions involving conventional Liquid Chromatography Mass Spectrometry (LC/MS) applications.

Abstract: The present invention provides methods for enhancing the fragmentation of peptides for mass spectrometry by modifying the peptides with a tagging reagent containing a functional group, such as a tertiary amine, having a greater gas-phase basicity than the amide backbone of the peptide. These high gas-phase basicity functional groups are attached to a peptide by reacting the tagging reagent to one or more available carboxylic acid groups of the peptide. Linking these high gas-phase functional groups to the peptides leads to higher charge state ions from electrospray ionization mass spectrometry (ESI-MS), which fragment more extensively during fragmentation techniques, particularly non-ergodic fragmentation techniques such as electron capture dissociation (ECD) and electron transfer dissociation (ETD).