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Discovery of Alternative Producers of the Enediyne Antitumor Antibiotic C-1027 with High Titers

18.01.2018 | Xiaohui Yan; Hindra; Huiming Ge; Dong Yang; Tingting Huang; Ivana Crnovcic; Chin-Yuan Chang; Shi-Ming Fang; Thibault ..., Journal of Natural Products, 2018

The potent cytotoxicity and unique mode of action make the enediyne antitumor antibiotic C-1027 an exquisite drug candidate for anticancer chemotherapy. However, clinical development of C-1027 has been hampered by its low titer from the original producer Streptomyces globisporus C-1027. Here we ...


Gastric Emptying and Small Bowel Water Content after Administration of Grapefruit Juice Compared to Water and Isocaloric Solutions of Glucose and Fructose: A Four-Way Crossover MRI Pilot Study in Healthy Subjects

18.01.2018 | Michael Grimm; Mirko Koziolek; Marwa Saleh; Felix Schneider; Grzegorz Garbacz; Jens-Peter Kühn; Werner Weitschies, Molecular Pharmaceutics, 2018

Grapefruit juice (GFJ) is known to affect the bioavailability of drugs in different ways. Despite the influence on gastrointestinal enzymes and transporters, the influence on gastrointestinal fluid kinetics is regarded to be relevant for the absorption of several drugs. Thus, it was the aim of ...


Targeted, Stimuli-Responsive Delivery of Plasmid DNA and miRNAs Using a Facile Self-Assembled Supramolecular Nanoparticle System

18.01.2018 | Li-Yen Wong; Bingzhao Xia; Ernst Wolvetang; Justin Cooper-White, Biomacromolecules, 2018

Gene therapy is rapidly regaining traction in terms of research activity and investment across the globe, with clear potential to revolutionize medicine and tissue regeneration. Viral vectors remain the most commonly utilized gene delivery vehicles, due to their high efficiency, however, they are ...


Injectable Hydrogel with Slow Degradability Composed of Gelatin and Hyaluronic Acid Cross-Linked by Schiff’s Base Formation

18.01.2018 | Takuro Hozumi; Tatsuto Kageyama; Seiichi Ohta; Junji Fukuda; Taichi Ito, Biomacromolecules, 2018

We developed an injectable gelatin/hyaluronic acid hydrogel with slow degradability, which consisted of carbohydrazide-modified gelatin (Gel-CDH) and hyaluronic acid monoaldehyde (HA-mCHO). Gel-CDH/HA-mCHO hydrogels were degraded much more slowly in phosphate-buffered saline than the other ...


Dual Allosteric Inhibition of SHP2 Phosphatase

18.01.2018 | Michelle Fodor; Edmund Price; Ping Wang; Hengyu Lu; Andreea Argintaru; Zhouliang Chen; Meir Glick; Huai-Xiang Hao; M ..., ACS Chemical Biology, 2018

SHP2 is a cytoplasmic protein tyrosine phosphatase encoded by the PTPN11 gene and is involved in cell proliferation, differentiation, and survival. Recently, we reported an allosteric mechanism of inhibition that stabilizes the auto-inhibited conformation of SHP2. SHP099 (1) was identified and ...


Chemical Control of a CRISPR-Cas9 Acetyltransferase

17.01.2018 | Jonathan H. Shrimp; Carissa Grose; Stephanie R. T. Widmeyer; Abigail L. Thorpe; Ajit Jadhav; Jordan L. Meier, ACS Chemical Biology, 2018

Lysine acetyltransferases (KATs) play a critical role in the regulation of transcription and other genomic functions. However, a persistent challenge is the development of assays capable of defining KAT activity directly in living cells. Toward this goal, here we report the application of a ...


Paralithocins, Antimicrobial Peptides with Unusual Disulfide Connectivity from the Red King Crab, Paralithodes camtschaticus

17.01.2018 | Morten K. Moe; Tor Haug; Magne O. Sydnes; Sigmund V. Sperstad; Chun Li; Lena C. Vaagsfjord; Enrique de la Vega; Klar ..., Journal of Natural Products, 2018

As part of an ongoing exploration of marine invertebrates as a source of new antimicrobial peptides, hemocyte extracts from the red king crab, Paralithodes camtschaticus, were studied. Three cationic cysteine (Cys)-rich peptides, named paralithocins 1–3, were isolated by bioassay-guided ...


Low-Density Lipoproteins and Human Serum Albumin as Carriers of Squalenoylated Drugs: Insights from Molecular Simulations

17.01.2018 | Semen O. Yesylevskyy; Christophe Ramseyer; Mariia Savenko; Simona Mura; Patrick Couvreur, Molecular Pharmaceutics, 2018

We have studied the interaction of three clinically promising squalenoylated drugs (gemcitabine-squalene, adenine-squalene, and doxorubicin-squalene) with low-density lipoproteins (LDL) by means of atomistic molecular dynamics simulations. It is shown that all studied squalenoylated drugs ...


Reconstitution of Kinamycin Biosynthesis within the Heterologous Host Streptomyces albus J1074

17.01.2018 | Xiangyang Liu; Dongxu Liu; Min Xu; Meifeng Tao; Linquan Bai; Zixin Deng; Blaine A. Pfeifer; Ming Jiang, Journal of Natural Products, 2018

Diazofluorene compounds such as kinamycin and lomaiviticin feature unique molecular structures and compelling medicinal bioactivities. However, a complete understanding of the biosynthetic details for this family of natural products has yet to be fully elucidated. In addition, a lack of ...


Hsp70 Inhibits the Nucleation and Elongation of Tau and Sequesters Tau Aggregates with High Affinity

17.01.2018 | Franziska Kundel; Suman De; Patrick Flagmeier; Mathew H. Horrocks; Magnus Kjaergaard; Sarah L. Shammas; Sophie E. Ja ..., ACS Chemical Biology, 2018

As a key player of the protein quality control network of the cell, the molecular chaperone Hsp70 inhibits the aggregation of the amyloid protein tau. To date, the mechanism of this inhibition and the tau species targeted by Hsp70 remain unknown. This is partly due to the inherent difficulty of ...


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