Applications of spermine or its pharmaceutically acceptable derivative in preparation of an SAICAR synthetase activity interfering agent or inhibitor. Applications of spermine or its pharmaceutically acceptable derivative in preparation of antitumor drug.

The invention provides methods and compositions for enhancing the efficacy of cancer therapies through modulation of BAL1 and/or BBAP. Also provided are methods for predicting the efficacy of cancer therapies or treating cancer in a subject through modulation of BAL1 and/or BBAP. Further provided are methods for identifying compounds that are capable of modulating BAL1-BBAP complexes.

The invention pertains to a method to identify an effective combination of a transmembrane E3 ubiquitin ligase and a membrane-bound protein, wherein the combination is effective when the transmembrane E3 ubiquitin ligase is capable of decreasing the surface level of the membrane-bound protein upon forced dimerization, preferably by ubiquitination of the membrane-bound protein. The method of the invention comprises a step of exposing a cell to a heterobifunctional molecule, wherein the heterobifunctional molecule comprises a first binding domain capable of specific binding to an extracellular portion of the transmembrane E3 ubiquitin ligase, and a second binding domain capable of specific binding to an extracellular portion of the membrane-bound protein. The method further comprises a step of determining the decrease in surface level of the membrane-bound protein. The invention additionally pertains to a heterobifunctional molecule targeting an effective combination of a transmembrane E3 ubiquitin ligase and a membrane-bound protein.

The present invention concerns compounds that are capable of covalently entrapping adenylating enzymes. The present invention is essentially based on the discovery that analogues of adenylating enzyme (AE) substrates, wherein a methylene group has been incorporated at the carbon atom in the α-position relative to the carboxylate group involved in the adenylation, are capable of undergoing the adenylation reaction, thereby creating an activated methylene group in situ. The resulting ‘armed’ acyladenylate can interact with the enzyme resulting in covalent entrapment. Interestingly, the acyladenylate can alternatively be transferred to the next step in the enzyme cascade, following which the activated methylene group can interact with the next (active site cysteine containing) enzyme in the enzymatic cascade. The AE substrate analogues, based on their capability of ‘entrapping’ the respective enzymes, will have utility as activity based probes in biological research and also as diagnostic and/or therapeutic agents.

A method of detecting a ligase expressing micro-organism in a sample comprises steps of treating the sample under conditions that inhibit the activity of ATP-dependent ligase from mammalian cells but which do not inhibit the activity of the microbial ligases, contacting the sample or a portion of the sample with a nucleic acid molecule which acts as a substrate for ligase activity in the sample, incubating the thus contacted sample under conditions suitable for ligase activity; and specifically determining the presence and/or the amount of a ligated nucleic acid molecule resulting from the action of the ligase on the substrate nucleic acid molecule to indicate the presence of the ligase expressing micro-organism. The micro-organism may be a fungus or a bacterium or both. High pH conditions may be employed to inactivate mammalian ligases. Related kits are described.

Provided are compositions comprising newly identified protein fragments of aminoacyl-tRNA synthetases, polynucleotides that encode them and complements thereof, related agents, and methods of use thereof in diagnostic, drug discovery, research, and therapeutic applications.

Cyclic-GMP-AMP (cGAMP), including 2′,3′-cGAMP, are used in pharmaceutical formulations (including vaccine adjuvants), drug screens, therapies and diagnostics.

The present invention relates to an antibody that specifically binds to the lysyl-tRNA synthase N-terminal domain exposed to the extracellular membrane, more specifically, it specifically binds to the lysyl-tRNA synthetase (KRS, Lysyl-tRNA synthetase)N-terminal domain exposed to the extracellular membrane having a specific CDR (complementarity determining region) sequence described herein, and relates to the use for the prevention, treatment or diagnosis of cancer, cancer metastasis, or diseases related to immune cell migration of a composition comprising an antibody or fragment thereof having high affinity and stability or the antibody and fragment thereof as an active ingredient. The method of the present invention can be usefully used to prepare an antibody having a higher affinity for the KRS N-terminus than a conventional antibody.

A method of conducting an enzymatic reaction assay involving adenosine 5′-monophosphate (AMP) comprising the steps of reacting one or more compounds and producing AMP, deaminating the AMP to produce IMP, and oxidating the IMP by NAD+ to produce XMP and NADH.

Life-threatening traumas such as terrorist attacks, war, disasters, mental or physical assault, severe accidents and violence frequently provoke emotional and behavioral disturbances known as post-traumatic stress disorder (PTSD) and suicide related thereto. Accurate diagnosis and treatment planning for PTSD and suicide remain difficult. The discovery of specific markers creates new opportunities for more accurate clinical assessments identifying groups that may experience better outcomes when exposed to an intervention. The present invention provides a process of detection of P-11, UBE3A, STY1, EMAP-II, SIP1, ORC5L, DCX, SCYE protein in a biological sample of a subject suspected of suffering from PTSD and/or having suicidal tendencies, and provides additional PTSD markers which are specific to gender.