通过光诱导环加成合成细胞通透性订书肽双抑制剂，用于 p53-Mdm2/Mdmx 相互作用。
Synthesis of cell-permeable stapled peptide dual inhibitors of the p53-Mdm2/Mdmx interactions via photoinduced cycloaddition.
机构信息
Department of Chemistry, State University of New York at Buffalo, Buffalo, NY 14260, USA.
出版信息
Bioorg Med Chem Lett. 2011 Mar 1;21(5):1472-5. doi: 10.1016/j.bmcl.2011.01.004. Epub 2011 Jan 7.
Abstract
We report the first application of a photoinduced 1,3-dipolar cycloaddition reaction to 'staple' a peptide dual inhibitor of the p53-Mdm2/Mdmx interactions. A series of stapled peptide inhibitors were efficiently synthesized and showed excellent dual inhibitory activity in ELISA assay. Furthermore, the positively charged, stapled peptides showed enhanced cellular uptake along with modest in vivo activity.
摘要
我们首次报道了光诱导 1,3-偶极环加成反应在“钉合”肽类 p53-Mdm2/Mdmx 相互作用双重抑制剂中的应用。一系列订书肽类抑制剂被高效合成，并在 ELISA 测定中表现出优异的双重抑制活性。此外，带正电荷的订书肽类化合物表现出增强的细胞摄取能力以及适度的体内活性。
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