Jadhav Pramodkumar D, Shen Jianheng, Sammynaiken Ramaswami, Reaney Martin J T
Plant Sciences, University of Saskatchewan, Saskatoon, SK (Canada).
Saskatchewan Structural Sciences Centre, University of Saskatchewan, Saskatoon, SK (Canada).
Chemistry. 2015 Nov 16;21(47):17023-34. doi: 10.1002/chem.201502699. Epub 2015 Oct 5.
Flax cyclic peptides (orbitides, linusorbs (LOs)) [1-8-NαC],[1-MetO2]-linusorb B1 ([MetO2]-LO1) and [1-9-NαC],[1-MetO2]-linusorb B2 ([MetO2]-LO2) are biologically active. These LOs lack active nuclei commonly used in peptide modification. We have developed reactions to activate methionine methyl sulphide to produce stable derivatives. In these reactions, LOs are converted to sulfonium intermediates and subsequently to derivatives containing active nuclei while preserving their fundamental structures. The reaction conditions preserved cyclic peptide fundamental structure and organic solvent solubility. [Met]-LO1 and [Met]-LO2 analogues containing activated groups (-CN, -COOEt, and -NH2 ) in the form of methionine, methionine (S)-oxide, and methionine (S,S)-dioxide amino acids were synthesized and characterized by LCMS and 1D and 2D NMR spectroscopy. Coumarin orbitide complexes produced in this manner bind Eu(3+) yielding FRET compounds that absorb energy through coumarin antennae and emit photons at lanthanide wavelengths.
亚麻环肽（环肽、亚麻环肽（LOs））[1-8-NαC]、[1-甲硫醚氧化物]-亚麻环肽B1（[甲硫醚氧化物]-LO1）和[1-9-NαC]、[1-甲硫醚氧化物]-亚麻环肽B2（[甲硫醚氧化物]-LO2）具有生物活性。这些LOs缺乏肽修饰中常用的活性基团。我们开发了激活甲硫醚以产生稳定衍生物的反应。在这些反应中，LOs转化为锍中间体，随后转化为含有活性基团的衍生物，同时保留其基本结构。反应条件保留了环肽的基本结构和在有机溶剂中的溶解性。合成了以甲硫氨酸、甲硫氨酸（S）-氧化物和甲硫氨酸（S，S）-二氧化物氨基酸形式含有活性基团（-CN、-COOEt和-NH2）的[甲硫氨酸]-LO1和[甲硫氨酸]-LO2类似物，并通过液相色谱-质谱联用仪以及一维和二维核磁共振光谱进行了表征。以这种方式产生的香豆素环肽配合物与Eu(3+)结合，产生荧光共振能量转移化合物，这些化合物通过香豆素天线吸收能量并在镧系元素波长处发射光子。
