NMR solution structure of the angiostatic peptide anginex.
NMR solution structure of the angiostatic peptide anginex.
复制标题
血管抑制肽 anginex 的 NMR 溶液结构。
DOI：
10.1016/j.bbapap.2007.03.007
复制
发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Mayo,KevinH
中科院分区：
文献类型：
--
作者：
Arroyo,MonicaM;Mayo,KevinH
Anginex是一种设计的33聚体肽，已知具有抗血管生成剂和杀菌剂的功能。解析多肽的核磁共振溶液结构是更好地理解其构效关系和设计更多具有生物活性的多肽和肽模拟物的关键。然而，由于亚基交换诱导的共振增宽，anginex的结构解析一直难以捉摸。在这里，我们发现，在胶束环境中进行NMR结构研究废除交换加宽，并允许anginex的结构被确定。Anginex以两亲性、三链反平行β折叠构象折叠，功能关键的疏水残基位于β折叠的一面，带正电荷，主要是赖氨酸残基位于相对面。与同源但相对无活性的肽βpep-28进行结构比较。这些结果有助于设计用于治疗血管生成相关疾病如癌症以及感染性疾病的anginex的肽模拟物。
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 β-sheet conformation with functionally key hydrophobic residues lying on one face of the β-sheet and positively charged, mostly lysine residues, lying on the opposite face. Structural comparison is made with a homologous, yet relatively inactive peptide, βpep-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.