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Archive - Feb 5, 2020

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New Route Developed for Synthesis of Deadly Mushroom Toxin Amanitin, Which Is Potentially Useful Therapeutically; Method May Allow Toxin to Be Produced at Industrial Scale, Thus Enabling Possibly Rapid Research Advances

The death cap mushroom (Amanita phalloides) is highly toxic. However, some of its toxins can also be healing when used appropriately: for instance, amanitins are potential components for antibody-based cancer treatments. In the journal Angewandte Chemie, German, in an article published online on December 17, 2019, scientists have now described a new synthetic route for α-amanitin. The open-access article is titled “A Convergent Total Synthesis of the Death Cap Toxin α‐Amanitin.” Their method seems suitable for production on a larger scale, finally making enough of the toxin available for further research. Amanitins inhibit the enzyme RNA polymerase II with high selectivity, which leads to cell death. When transported into tumor cells by antibodies, the toxin could fight tumors. Until recently, however, the only source of amanitins was the mushrooms (Amanita phalloides) themselves, which limited the possibilities for experimentation. Some time ago, a total synthesis was reported for α-amanitin, the most powerful amanitin. Researchers working with Roderich D. Süssmuth, PhD, at the Technical University of Berlin have now introduced an alternative route for a total synthesis that occurs entirely in the liquid phase, allows for the possibility of producing different structural variants, and can be implemented on a larger scale. “We decided to use a convergent route, meaning that several components are first synthesized independently and then finally put together to form the target molecule,” explains Dr. Süssmuth. The building blocks are three peptide fragments made of five, one, and two amino acids. The researchers refer to their method as a [5+1+2] synthesis.

Unlocking the Secrets of Cell Regulation: Researches at University of Bonn Investigate Structure of Long RNAs; Develop New Method to Accurately Measure RNA Lengths

Ribonucleic acids (RNA) ensure that the blueprint in the cell nucleus is translated into vital proteins and that cell functions are regulated. However, little is known about the structure and function of particularly long RNAs, which consist of hundreds or thousands of building blocks. Chemists at the University of Bonn have now developed a new method for this purpose: They mark the complex molecules with tiny "flags" and measure the distances between them with a "molecular ruler". The results are published online on January 25, 2020 in Angewandte Chemie International Edition. The article is titled “EPR Distance Measurements on Long Non-Coding RNAs Empowered by Genetic Alphabet Expansion Transcription.” In living cells, everything follows a plan: The blueprints for all building and operating materials are stored in the cell nucleus. If, for example, a certain protein is required, the genetic information is read from the DNA and translated into ribonucleic acid (RNA). The RNA transmits the blueprint to the cell's "protein factories", the ribosomes. "However, more than 80 percent of ribonucleic acids are not involved in the production of proteins at all," says Dr. Stephanie Kath-Schorr (photo) from the LIMES Institute at the University of Bonn. This so-called "non-coding" RNA is probably involved in various regulatory processes in the cell. Scientists would like to gain a much better understanding of the control processes that non-coding RNA is responsible for. "To do this, however, we must first understand the structures of ribonucleic acids and how they are folded," says Kath-Schorr. The spatial structure seems to have an important role in the function of RNA. It determines which molecules a certain RNA binds to and therefore triggers important processes in the cell.

Scientists Find Long Non-Coding RNA (lncRNA) Affecting Skin Cancer Progression; PRECSIT lncRNA Promotes Growth & Spread of Cutaneous Squamous Cell Carcinoma

Researchers at the University of Turku, Turku University Central Hospital, and Western Cancer Center (FICAN West) have discovered a newly identified long non-coding (lnc) RNA molecule (PRECSIT) that regulates the growth and invasion of squamous cell carcinoma of the skin. In the future, PRECSIT lnc RNA could potentially serve as a new marker for the detection of rapidly advancing or spreading squamous cell carcinoma and as a target for new therapies. Skin cancers are the most common cancers in the world and their incidence is increasing. Squamous cell carcinoma is the most common metastatic skin cancer and its incidence is increasing worldwide. Long-term exposure to the sun's ultraviolet radiation is the most important risk factor for the development of this type of cancer. Squamous cell carcinoma of the skin is characterized by a significant gene mutation burden of cancer cells resulting from long-term exposure to the sun's ultraviolet radiation. Several gene mutations predisposing to skin cancer are known, but the importance of non-coding RNA molecules of the so-called dark side of the genome in the development of squamous cell carcinoma is still unclear, says Professor Veli-Matti Kähäri, MD, PhD, from the Department of Dermatology at the University of Turku in Finland. The majority of the human genome contains genes that do not produce protein, but their role as regulators of cellular functions is still essential. Long non-coding RNAs (lncRNAs) are a largely unknown set of RNAs and recent studies have found that they play a role in regulating signaling pathways, particularly in cancer, says researcher Minna Piipponen, PhD, one of the authors of the study. Thus, RNA molecules could be utilized in cancer diagnostics as specific marker molecules and as targets for new therapies.