866363-70-4Relevant articles and documents
SiO2 nanoparticles as platform for delivery of nucleoside triphosphate analogues into cells
Vasilyeva, Svetlana V.,Silnikov, Vladimir N.,Shatskaya, Natalia V.,Levina, Asya S.,Repkova, Marina N.,Zarytova, Valentina F.
, p. 703 - 711 (2013)
A system for delivery of analogues of 2′-deoxyribonucleoside triphosphate (dNTP) based on SiO2 nanoparticles was proposed. A simple and versatile method was developed for the preparation of SiO 2-dNTP conjugates using the 'click'-reaction between premodified nanoparticles containing the azido groups and dNTP containing the alkyne-modified γ-phosphate group. The substrate properties of SiO 2-dNTP were tested using Klenow fragment and HIV reverse transcriptase. Nucleoside triphosphates being a part of the SiO2-dNTP nanocomposites were shown to be incorporated into the growing DNA chain. The rate of polymerization with the use of SiO2-dNTP or common dNTP in case of HIV reverse transcriptase differed insignificantly. It was shown by confocal microscopy that the proposed SiO2-dNTP nanocomposites bearing the fluorescent label penetrate into cells and even into cellular nuclei.
Intracellular Delivery of Functional Native Antibodies under Hypoxic Conditions by Using a Biodegradable Silica Nanoquencher
Yuan, Peiyan,Zhang, Hailong,Qian, Linghui,Mao, Xin,Du, Shubo,Yu, Changmin,Peng, Bo,Yao, Shao Q.
, p. 12481 - 12485 (2017)
Antibodies are important biopharmaceuticals, but almost all existing antibody-based drugs are limited to targeting antigens located at the cell exterior because of the inability of antibodies to enter the cell interior. Available methods for intracellular
Simultaneous Imaging of Endogenous Survivin mRNA and On-Demand Drug Release in Live Cells by Using a Mesoporous Silica Nanoquencher
Yuan, Peiyan,Mao, Xin,Chong, Kok Chan,Fu, Jiaqi,Pan, Sijun,Wu, Shuizhu,Yu, Changmin,Yao, Shao Q.
, (2017)
The design of multifunctional drug delivery systems capable of simultaneous target detection, imaging, and therapeutics in live mammalian cells is critical for biomedical research. In this study, by using mesoporous silica nanoparticles (MSNs) chemically modified with a small-molecule dark quencher, followed by sequential drug encapsulation, MSN capping with a dye-labeled antisense oligonucleotide, and bioorthogonal surface modification with cell-penetrating poly(disulfide)s, the authors have successfully developed the first mesoporous silica nanoquencher (qMSN), characterized by high drug-loading and endocytosis-independent cell uptake, which is able to quantitatively image endogenous survivin mRNA and release the loaded drug in a manner that depends on the survivin expression level in tumor cells. The authors further show that this novel drug delivery system may be used to minimize potential cytotoxicity encountered by many existing small-molecule drugs in cancer therapy.
MULTI-FUNCTIONAL CHIMERIC MOLECULES
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Paragraph 0028; 0080, (2021/07/17)
The present disclosure relates to multifunctional chemical conjugation molecules, which find utility as modifiers of target substrates. The present disclosure includes multifunctional compounds comprising a localizing moiety, a chemical linker moiety, an activator moiety, a first orienting adaptor interconnecting the chemical linker moiety on one end to the activator moiety, and optionally a second orienting adaptor interconnecting the chemical linker molecule on a different end to the localizing moiety. Molecules according to the present invention find use making post-translational modifications to macromolecules that are not the natural substrate of the activator moiety. Diseases or disorders may be treated or prevented with molecules of the present disclosure.
Phosphorylation-Inducing Chimeric Small Molecules
Siriwardena, Sachini U.,Munkanatta Godage, Dhanushka N. P.,Shoba, Veronika M.,Lai, Sophia,Shi, Mengchao,Wu, Peng,Chaudhary, Santosh K.,Schreiber, Stuart L.,Choudhary, Amit
supporting information, p. 14052 - 14057 (2020/09/02)
Small molecules have been classically developed to inhibit enzyme activity; however, new classes of small molecules that endow new functions to enzymes via proximity-mediated effect are emerging. Phosphorylation (native or neo) of any given protein-of-interest can alter its structure and function, and we hypothesized that such modifications can be accomplished by small molecules that bring a kinase in proximity to the protein-of-interest. Herein, we describe phosphorylation-inducing chimeric small molecules (PHICS), which enable two example kinases - AMPK and PKC - to phosphorylate target proteins that are not otherwise substrates for these kinases. PHICS are formed by linking small-molecule binders of the kinase and the target protein, and exhibit several features of a bifunctional molecule, including the hook-effect, turnover, isoform specificity, dose and temporal control of phosphorylation, and activity dependent on proximity (i.e., linker length). Using PHICS, we were able to induce native and neo-phosphorylations of BRD4 by AMPK or PKC. Furthermore, PHICS induced a signaling-relevant phosphorylation of the target protein Bruton's tyrosine kinase in cells. We envision that PHICS-mediated native or neo-phosphorylations will find utility in basic research and medicine.
