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    Synthetic opioid vaccine
    34.
    发明授权
    Synthetic opioid vaccine 有权

    公开(公告)号：US11305010B2

    公开(公告)日：2022-04-19

    申请号：US16071199

    申请日：2017-01-18

    Applicant: THE SCRIPPS RESEARCH INSTITUTE

    Inventor： Kim D. Janda

    IPC: A61K31/385 ,  A61K47/64 ,  A61P25/30 ,  A61K47/68 ,  A61K39/00 ,  A61K39/395 ,  A61K39/385

    Abstract: Fentanyl is an addictive prescription opioid that is over 80 times mora potent than morphine. The synthetic nature of fentanyl has enabled the creation of dangerous “designer drug’ analogues that escape toxicology screening, yet display comparable potency to the parent drug. Alarmingly, a large number of fatalities have been linked to overdose of fentanyl derivatives. Herein, we report an effective immunotherapy for reducing the psychoactive effects of fentanyl class drugs. A single conjugate vaccine was created that elicited high levels of antibodies with cross-reactivity for a wide panel of fentanyl analogues, Moreover, vaccinated mice gained significant protection from lethal fentanyl doses. Lastly, a surface plasmon resonance (SPR)-based technique was established enabling drug specificity profiling of antibodies derived directly from serum. Our newly developed fentanyl vaccine and analytical methods may assist in the battle against synthetic opioid abuse.

    CU-AND NI-CATALYZED DECARBOXYLATIVE BORYLATION REACTIONS
    38.
    发明申请
    CU-AND NI-CATALYZED DECARBOXYLATIVE BORYLATION REACTIONS 有权

    公开(公告)号：US20220024949A1

    公开(公告)日：2022-01-27

    申请号：US17449509

    申请日：2021-09-30

    Applicant: The Scripps Research Institute

    Inventor： Phil Baran ,  Chao Li ,  Jie Wang ,  Amab K. Chatterjee ,  Manoj Kumar ,  Shan Yu ,  Kristen Johnson ,  Tian Qin ,  Ming Shang

    IPC: C07F5/02 ,  B01J31/02 ,  C07B47/00 ,  C07K7/64

    Abstract: The invention is directed to methods of converting a carboxylic acid group in a compound, via a redox active ester, to a corresponding boronic ester by treatment with bis(pinacolato)diboron-alkyllithium complex in the presence of a ligand, a Ni(II) salt or a copper salt, and an Mg(II) salt, in the presence of an alkyllithium or a lithium hydroxide or alkoxide salt. The product pinacolato boronate ester can be cleaved to provide a boronic acid. The invention is also directed to methods of preparing various compounds of medical value comprising boronic acid groups, and to novel boronic-acid containing compounds of medicinal value, including an atorvastatin boronic acid analog, a vancomycin aglycone boronic acid analog, and boronic acid containing elastase inhibitors mCBK319, mCBK320, mCBK323, and RPX-7009.

    INDUCTION OF PLURIPOTENT CELLS
    39.
    发明申请
    INDUCTION OF PLURIPOTENT CELLS 有权

    公开(公告)号：US20210403878A1

    公开(公告)日：2021-12-30

    申请号：US17320676

    申请日：2021-05-14

    Applicant: The Scripps Research Institute

    Inventor： Tongxiang Lin ,  Sheng Ding

    IPC: C12N5/074

    Abstract: The slow kinetics and low efficiency of reprogramming methods to generate human induced pluripotent stem cells (iPSCs) impose major limitations on their utility in biomedical applications. Here we describe a chemical approach that dramatically improves (>200 fold) the efficiency of iPSC generation from human fibroblasts, within seven days of treatment. This will provide a basis for developing safer, more efficient, non-viral methods for reprogramming human somatic cells.

    TARGET VALIDATION AND PROFILING OF THE RNA TARGETS OF SMALL MOLECULES
    40.
    发明申请
    TARGET VALIDATION AND PROFILING OF THE RNA TARGETS OF SMALL MOLECULES 有权

    公开(公告)号：US20210379188A1

    公开(公告)日：2021-12-09

    申请号：US17284297

    申请日：2019-09-26

    Applicant: The Scripps Research Institute

    Inventor： Matthew D. Disney

    IPC: A61K47/55 ,  C12N15/11 ,  A61K31/704

    Abstract: A method for the precise cellular destruction of an oncogenic non-coding RNA with a RNA-binding small molecule conjugated with bleomycin A5 is described. The method affords reversal of phenotype. Bleomycin A5 was coupled to an RNA-binding molecule that selectively binds the microRNA-96 hairpin precursor (pri-miR-96). By coupling of bleomycin A5's free amine to the RNA-binding molecule, its affinity for binding to pri-miR-96 is >100-fold stronger than to DNA. The conjugate compound selectively cleaves pri-miR-96 in triple negative breast cancer (TNBC) cells. Selective cleavage of pri-miR-96 enhances expression of FOXO1 protein, a pro-apoptotic transcription factor that miR-96 silences, and triggers apoptosis in TNBC cells. No effects were observed in healthy breast epithelial cells. This method provides programmable control for targeting RNA through the selection of an RNA-binding molecule/bleomycin A5 conjugate and provides a facile method of mapping the cellular binding sites of an RNA-binding molecule.

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