Walker Susanne N, Tennyson Rachel L, Chapman Alex M, Kennan Alan J, McNaughton Brian R
Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins, CO 80523 (USA).
Chembiochem. 2015 Jan 19;16(2):219-22. doi: 10.1002/cbic.201402531. Epub 2014 Dec 4.
Methods for the stabilization of well-defined helical peptide drugs and basic research tools have received considerable attention in the last decade. Here, we report the stable and functional display of an HIV gp41 C-peptide helix mimic on a GRAM-Like Ubiquitin-binding in EAP45 (GLUE) protein. C-peptide helix-grafted GLUE selectively binds a mimic of the N-terminal helical region of gp41, a well-established HIV drug target, in a complex cellular environment. Additionally, the helix-grafted GLUE is folded in solution, stable in human serum, and soluble in aqueous solutions, and thus overcomes challenges faced by a multitude of peptide drugs, including those derived from HIV gp41 C-peptide.
在过去十年中,用于稳定明确的螺旋肽药物和基础研究工具的方法受到了相当多的关注。在此,我们报告了HIV gp41 C肽螺旋模拟物在EAP45中类GRAM泛素结合蛋白(GLUE)上的稳定且功能性展示。C肽螺旋嫁接的GLUE在复杂的细胞环境中选择性地结合gp41 N端螺旋区域的模拟物,gp41是一个成熟的HIV药物靶点。此外,螺旋嫁接的GLUE在溶液中折叠,在人血清中稳定,且可溶于水溶液,因此克服了多种肽药物所面临的挑战,包括那些源自HIV gp41 C肽的药物。