![]() Although these peptides show better selectivity towards the Kv1.3 channel than chemical molecules, they usually also inhibit some highly similar potassium channel subtypes 9, 10, 11, 12. To date, a large number of toxin peptides have been shown to inhibit the Kv1.3 channel at picomolar to nanomolar concentrations 9. Due to the inherent poor selectivity and potential side effects of previously reported chemical molecules targeting the Kv1.3 channel 4, 5, considerable attention has been paid to the discovery of peptide drugs recently.ĭuring long-term molecular evolution, venoms from different species, such as scorpion, sea anemone, snake and cone snail, have become a well-known resource for peptide blockers that target the Kv1.3 channel 6, 7, 8. Kv1.3 channel blockers suppressed cytokine secretion and alleviated diseases in animal models of T cell-mediated autoimmune diseases 1, 3. The voltage-gated Kv1.3 potassium channel is expressed in effector memory T cells and has been proven to be an attractive drug target for the treatment of various autoimmune diseases 1, 2. Together, these findings indicate not only the promising prospect of BmKTX-19 and BmKTX-196 as drug candidates but also the desirable feasibility of the evolution-guided peptide drug design for discovering numerous peptide drugs for the Kv1.3 channel. In addition to the structural similarity between the designed and native peptides, both experimental alanine-scanning mutagenesis and computational simulation further indicated that the binding interface of wild-type BmKTX was successfully reoriented in BmKTX-19 and BmKTX-196, which adopted distinct toxin surfaces as binding interfaces. Pharmacological experiments indicated that BmKTX-19 and BmKTX-196 peptides were specific inhibitors of the Kv1.3 channel and effectively suppressed cytokine secretion. Using a natural basic toxin, BmKTX, as a template, which contains 2 acidic residues (Asp19 and Asp33), we engineered two new peptides BmKTX-19 with 1 acidic residue (Asp33), and BmKTX-196 with 2 acidic residues (Asp6 and Asp33) through only adjusting acidic residue distribution for reorientation of BmKTX binding interface. Based on the evolutionary function of toxin acidic residues, de novo peptide drugs with distinct binding interfaces were designed for the immunotherapeutic target, the Kv1.3 channel. The restaurant plans to serve lunch, dinner, and a Sunday brunch when it opens in May.During the long-term evolution of animal toxins acting on potassium channels, the acidic residues can orientate the toxin binding interfaces by adjusting the molecular polarity. A sliding glass door opens to the outdoor patio. The space will have a dark look with splashes of color and “Instagrammable moments” with neon signs and wallpaper throughout. Altschul says some new dishes, such as a wagyu hot rock, focus on presentation and how the dish arrives at the table.īut later at night, the restaurant gets a little darker and turns into more of a “social lounge,” especially Thursdays through Saturdays. The menu features dishes such as king crab tempura, fried rice with duck or lobster, crispy honey chicken, Mongolian steak, some wok dishes, hamachi, and yellowtail jalapeño yuzu. He works with Charlie Huang, owner of his eponymous restaurant group and a former protege of chef Akira Back. “We’re taking inspiration from the new spots around the Strip such as Yellowtail and Catch,” Altschul says. Spencer Altschul, the vice president of operations for Jing, says this location will be a little different from the locations in Greenwood Village and Aspen by incorporating a nightlife feel to the space. Now the restaurant that converts into a lounge on the weekends plans to open in the former 8,600-square-foot Fogo de Chao Brazilian Steakhouse space at Downtown Summerlin. For more than a decade, Jing has served Asian fusion dishes that span sushi to steaks in Denver. ![]()
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