Arroyo Monica M, Mayo Kevin H
Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota Health Sciences Center, 6-155 Jackson Hall, 321 Church Street, Minneapolis, MN 55455, USA.
Biochim Biophys Acta. 2007 May;1774(5):645-51. doi: 10.1016/j.bbapap.2007.03.007. Epub 2007 Mar 24.
Anginex, a designed peptide 33mer, is known to function both as an antiangiogenic and bactericidal agent. Solving the NMR solution structure of the peptide is key to understand better its structure-activity relationships and to design more bioactive peptides and peptide mimetics. However, structure elucidation of anginex has been elusive due to subunit exchange-induced resonance broadening. Here, we found that performing NMR structural studies in a micellar environment abolishes exchange broadening and allows the structure of anginex to be determined. Anginex folds in an amphipathic, three-stranded antiparallel beta-sheet conformation with functionally key hydrophobic residues lying on one face of the beta-sheet and positively charged, mostly lysine residues, lying on the opposite face. Structural comparison is made with a homologous, yet relatively inactive peptide, betapep-28. These results contribute to the design of peptidomimetics of anginex for therapeutic use against angiogenically-related diseases like cancer, as well as infectious diseases.
血管抑制素（Anginex）是一种设计合成的33肽，已知它兼具抗血管生成和杀菌作用。解析该肽的核磁共振（NMR）溶液结构是更好地理解其构效关系以及设计更具生物活性的肽和肽模拟物的关键。然而，由于亚基交换导致共振峰变宽，血管抑制素的结构解析一直难以实现。在此，我们发现，在胶束环境中进行NMR结构研究可消除交换加宽现象，并能确定血管抑制素的结构。血管抑制素折叠成两亲性的三链反平行β-折叠构象，其功能关键的疏水残基位于β-折叠的一侧，而带正电荷的残基（大多为赖氨酸残基）位于另一侧。我们将其与同源但相对无活性的肽β-肽-28进行了结构比较。这些结果有助于设计血管抑制素的肽模拟物，用于治疗与血管生成相关的疾病（如癌症）以及传染病。
