RTD-1Mimic Containing 纬PNA Scaffold Exhibits Broad-Spectrum Antibacterial Activities

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• 作者：Srinivas Rapireddy ; Linda Nhon ; Robert E. Meehan ; Jonathan Franks ; Donna Beer Stolz ; Dat Tran ; Michael E. Selsted ; Danith H. Ly
• 刊名：The Journal of the American Chemical Society
• 出版年：2012
• 出版时间：March 7, 2012
• 年：2012
• 卷：134
• 期：9
• 页码：4041-4044
• 全文大小：290K
• 年卷期：v.134,no.9(March 7, 2012)
• ISSN：1520-5126

文摘

Macrocyclic peptides with multiple disulfide cross-linkages, such as those produced by plants and those found in nonhuman primates, as components of the innate immunity, hold great promise for molecular therapy because of their broad biological activities and high chemical, thermal, and enzymatic stability. However, for some, because of their intricate spatial arrangement and elaborate interstrand cross-linkages, they are difficult to prepare de novo in large quantities and high purity, due to the nonselective nature of disulfide-bond formation. We show that the disulfide bridges of RTD-1, a member of the 胃-defensin subfamily, could be replaced with noncovalent Watson鈥揅rick hydrogen bonds without significantly affecting its biological activities. The work provides a general strategy for engineering conformationally rigid, cyclic peptides without the need for disulfide-bond reinforcement.