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- W4386704328 abstract "Following a rational design, a series of macrocyclic (stapled) peptidomimetics of 10Panx1, the most established peptide inhibitor of Pannexin1 (Panx1) channels, were developed and synthesized. Two macrocyclic analogues SBL-PX1-42 and SBL-PX1-44 outperformed the linear native peptide. During in vitro adenosine triphosphate (ATP) release and Yo-Pro-1 uptake assays in a Panx1-expressing tumor cell line, both compounds were revealed to be promising bidirectional inhibitors of Panx1 channel function, able to induce a two-fold inhibition, as compared to the native 10Panx1 sequence. The introduction of triazole-based cross-links within the peptide backbones increased helical content and enhanced in vitro proteolytic stability in human plasma (>30-fold longer half-lives, compared to 10Panx1). In adhesion assays, a double-stapled peptide, SBL-PX1-206 inhibited ATP release from endothelial cells, thereby efficiently reducing THP-1 monocyte adhesion to a TNF-α-activated endothelial monolayer and making it a promising candidate for future in vivo investigations in animal models of cardiovascular inflammatory disease." @default.
- W4386704328 created "2023-09-14" @default.
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- W4386704328 date "2023-09-13" @default.
- W4386704328 modified "2023-10-18" @default.
- W4386704328 title "Structure-Based Design and Synthesis of Stapled <sup>10</sup>Panx1 Analogues for Use in Cardiovascular Inflammatory Diseases" @default.
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