949894-57-9Relevant academic research and scientific papers
Oligocholate foldamer with 'prefolded' macrocycles for enhanced folding in solution and surfactant micelles
Li, Xueshu,Zhao, Yan
, p. 6051 - 6059 (2013)
A cholate oligomer was synthesized with six linear cholate groups sandwiched by two tricholate macrocycles at the two termini. Two pyrenyl labels on the compound allowed its conformation to be studied by fluorescence spectroscopy. The linear/macrocyclic h
Proteasome Subunit Selective Activity-Based Probes Report on Proteasome Core Particle Composition in a Native Polyacrylamide Gel Electrophoresis Fluorescence-Resonance Energy Transfer Assay
De Bruin, Gerjan,Xin, Bo-Tao,Florea, Bogdan I.,Overkleeft, Herman S.
, p. 9874 - 9880 (2016)
Most mammalian tissues contain a single proteasome species: constitutive proteasomes. Tissues able to express, next to the constitutive proteasome catalytic activities (β1c, β2c, β5c), the three homologous activities, β1i, β2i and β5i, may contain numerous distinct proteasome particles: immunoproteasomes (composed of β1i, β2i and β5i) and mixed proteasomes containing a mix of these activities. This work describes the development of new subunit-selective activity-based probes and their use in an activity-based protein profiling assay that allows the detection of various proteasome particles. Tissue extracts are treated with subunit-specific probes bearing distinct fluorophores and subunit-specific inhibitors. The samples are resolved by native polyacrylamide gel electrophoresis, after which fluorescence-resonance energy transfer (FRET) reports on the nature of proteasomes present.
Alkyne Ligation Handles: Propargylation of Hydroxyl, Sulfhydryl, Amino, and Carboxyl Groups via the Nicholas Reaction
Wells, Sarah M.,Widen, John C.,Harki, Daniel A.,Brummond, Kay M.
, p. 4566 - 4569 (2016)
The Nicholas reaction has been applied to the installation of alkyne ligation handles. Acid-promoted propargylation of hydroxyl, sulfhydryl, amino, and carboxyl groups using dicobalt hexacarbonyl-stabilized propargylium ions is reported. This method is us
Immunoproteasome Inhibitor-Doxorubicin Conjugates Target Multiple Myeloma Cells and Release Doxorubicin upon Low-Dose Photon Irradiation
Dekker, Patrick M.,Florea, Bogdan I.,Maiorana, Santina,Maurits, Elmer,Neefjes, Jacques J. C.,Overkleeft, Herman S.,Van De Graaff, Michel J.,Van Der Zanden, Sabina Y.,Van Kasteren, Sander I.,Wander, Dennis P. A.
, p. 7250 - 7253 (2020/08/06)
Proteasome inhibitors are established therapeutic agents for the treatment of hematological cancers, as are anthracyclines such as doxorubicin. We here present a new drug targeting approach that combines both drug classes into a single molecule. Doxorubicin was conjugated to an immunoproteasome-selective inhibitor via light-cleavable linkers, yielding peptide epoxyketone-doxorubicin prodrugs that remained selective and active toward immunoproteasomes. Upon cellular uptake and immunoproteasome inhibition, doxorubicin is released from the immunoproteasome inhibitor through photoirradiation. Multiple myeloma cells in this way take a double hit: immunoproteasome inhibition and doxorubicin-induced toxicity. Our strategy, which entails targeting of a cytotoxic agent, through a covalent enzyme inhibitor that is detrimental to tumor tissue in its own right, may find use in the search for improved anticancer drugs.
General Strategy for Integrated Bioorthogonal Prodrugs: Pt(II)-Triggered Depropargylation Enables Controllable Drug Activation in Vivo
Sun, Tao,Lv, Tian,Wu, Jianbing,Zhu, Mingchao,Fei, Yue,Zhu, Jie,Zhang, Yihua,Huang, Zhangjian
, p. 13899 - 13912 (2020/12/02)
Bioorthogonal decaging reactions for controllable drug activation within complex biological systems are highly desirable yet extremely challenging. Herein, we find a new class of Pt(II)-triggered bioorthogonal cleavage reactions in which Pt(II) but not Pt(IV) complexes effectively trigger the cleavage of O/N-propargyl in a variety of ranges of caged molecules under biocompatible conditions. Based on these findings, we propose a general strategy for integrated bioorthogonal prodrugs and accordingly design a prodrug 16, in which a Pt(IV) moiety is covalently connected with an O2-propargyl diazeniumdiolate moiety. It is found that 16 can be specifically reduced by cytoplasmic reductants in human ovarian cancer cells to liberate cisplatin, which subsequently stimulates the cleavage of O2-propargyl to release large amounts of NO in situ, thus generating synergistic and potent tumor suppression activity in vivo. Therefore, Pt(II)-triggered depropargylation and the integration concept might provide a general strategy for broad applicability of bioorthogonal cleavage chemistry in vivo.
Precursor-Directed Diversification of Cyclic Tetrapeptidic Pseudoxylallemycins
Guo, Huijuan,Schmidt, Alexander,Stephan, Philipp,Ragu?, Luka,Braga, Daniel,Kaiser, Marcel,Dahse, Hans-Martin,Weigel, Christiane,Lackner, Gerald,Beemelmanns, Christine
, p. 2307 - 2311 (2018/10/15)
Cyclic peptides containing non-proteinogenic amino acids often exhibit a broad bioactivity spectrum and many have entered clinical trials with good prospects for drug development. We recently reported the discovery of six cyclic tetrapeptides, pseudoxylallemycins A–F (1–6), from a termite-associated Pseudoxylaria sp. X802. These compounds contain a rare O-homoallenyl-l-tyrosine moiety and show promising antimicrobial activity against the Gram-negative pathogenic bacterium Pseudomonas aeruginosa. To perform more detailed structure–activity studies, we pursued a precursor-directed diversification strategy. Herein, we report the purification, identification, and testing of 21 new pseudoxylallemycin derivatives.
Palladium-Triggered Chemical Rescue of Intracellular Proteins via Genetically Encoded Allene-Caged Tyrosine
Wang, Jie,Zheng, Siqi,Liu, Yanjun,Zhang, Zhaoyue,Lin, Zhi,Li, Jiaofeng,Zhang, Gong,Wang, Xin,Li, Jie,Chen, Peng R.
supporting information, p. 15118 - 15121 (2016/12/06)
Chemical de-caging has emerged as an attractive strategy for gain-of-function study of proteins via small-molecule reagents. The previously reported chemical de-caging reactions have been largely centered on liberating the side chain of lysine on a given protein. Herein, we developed an allene-based caging moiety and the corresponding palladium de-caging reagents for chemical rescue of tyrosine (Tyr) activity on intracellular proteins. This bioorthogonal de-caging pair has been successfully applied to unmask enzymatic Tyr sites (e.g., Y671 on Taq polymerase and Y728 on Anthrax lethal factor) as well as the post-translational Tyr modification site (Y416 on Src kinase) in vitro and in living cells. Our strategy provides a general platform for chemical rescue of Tyr-dependent protein activity inside cells.
Methods and compositions for labeling polypeptides
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Page/Page column 55, (2016/04/05)
Synthesis of many proteins is tightly controlled at the level of translation and plays an essential role in fundamental processes such as cell growth and proliferation, signaling, differentiation or death. Methods that allow imaging and identification of
MACROCYCLIC COMPOUNDS FOR INHIBITION OF INHIBITORS OF APOPTOSIS
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Page/Page column, (2014/05/20)
There are disclosed compounds that modulate the activity of inhibitors of apoptosis (IAPs), pharmaceutical compositions containing said compounds and methods of treating proliferative disorders and disorders of dysregulated apoptosis, such as cancer, util
MACROCYCLIC COMPOUNDS FOR INHIBITION OF INHIBITORS OF APOPTOSIS
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Page/Page column 48; 49, (2014/05/24)
There are disclosed compounds that modulate the activity of inhibitors of apoptosis (IAPs), pharmaceutical compositions containing said compounds and methods of treating proliferative disorders and disorders of dysregulated apoptosis, such as cancer, utilizing the compounds of the invention.
