Saweczko P, Enright G D, Kraatz H B
Department of Chemistry, University of Saskatchewan, 110 Science Place, Saskatoon, Saskatchewan S7N 5C9, Canada.
Inorg Chem. 2001 Aug 13;40(17):4409-19. doi: 10.1021/ic010145m.
The use of 3-aminopyrazole derivatives as beta-sheet templates is investigated using a series of ferrocenoyl (Fc)-dipeptides (Fc-Gly(2)-OEt, Fc-Ala(2)-OBzl, Fc-Leu-Phe-OMe, Fc-Val-Phe-OMe, Fc-Phe(2)-OMe, Fc-Leu(2)-OMe, Fc-Val(2)-OMe). The synthesis and full characterization are reported. The solid-state structures of Fc-Gly(2)-OMe and Fc-Leu-Phe-OMe show extensive hydrogen bonding of the podand peptide substituents, resulting in the formation of supramolecular Fc-dipeptide assemblies. For Fc-Gly(2)-OMe, this can be described as a parallel beta-sheet, whereas intermolecular interactions in Fc-Leu-Phe-OMe result in the formation of supramolecular helical structures. The saturation titrations of Fc-dipeptides with 3-amino-5-methylpyrazole (3-AMP) and 3-trifluoroacetylamido-5-methylpyrazole (3-TFAc-AMP) show a 1:1 interaction of the Fc-peptide with the aminopyrazole derivatives. IR measurements in solution confirm binding to the top face of the Fc-dipeptide and the involvement of the Fc-C=O and the ester C=O groups in establishing H-bonding interactions with the 3-TFAc-AMP. However, binding constants in chloroform are low and range from 8 to 27 M(-1), which correspond to binding energies of 5-7 kJ mol(-1). In higher polarity solvents, such as acetonitrile or acetone, the binding constants are below 5 M(-1), emphasizing the limited utility of 3-AMP derivatives as beta-sheet templates. Electrochemical measurements confirm the weak interactions between the various Fc-dipeptides and 3-TFAc-AMP. Typical shifts in the redox potential of the Fc moiety are in the range 0-20 mV. Attempts to modify 3-AMP at the 3-position by carbodiimide coupling with amino acid derivatives and, thus, enhance the binding to the Fc-peptides resulted in 2-amino acid substituted 3-AMP derivatives. Substitution at the 2-position blocks the binding site, and no interactions with Fc-dipeptides are observed.
使用一系列二茂铁酰基（Fc）-二肽（Fc-Gly(2)-OEt、Fc-Ala(2)-OBzl、Fc-Leu-Phe-OMe、Fc-Val-Phe-OMe、Fc-Phe(2)-OMe、Fc-Leu(2)-OMe、Fc-Val(2)-OMe）研究了3-氨基吡唑衍生物作为β-折叠模板的用途。报道了其合成及全面表征。Fc-Gly(2)-OMe和Fc-Leu-Phe-OMe的固态结构显示配体肽取代基存在广泛的氢键作用，导致形成超分子Fc-二肽组装体。对于Fc-Gly(2)-OMe，这可描述为平行β-折叠，而Fc-Leu-Phe-OMe中的分子间相互作用导致形成超分子螺旋结构。用3-氨基-5-甲基吡唑（3-AMP）和3-三氟乙酰氨基-5-甲基吡唑（3-TFAc-AMP）对Fc-二肽进行饱和滴定，结果显示Fc-肽与氨基吡唑衍生物存在1:1的相互作用。溶液中的红外测量证实其与Fc-二肽的顶面结合，且Fc-C=O和酯C=O基团参与与3-TFAc-AMP建立氢键相互作用。然而，在氯仿中的结合常数较低，范围为8至27 M(-1)，对应于5-7 kJ mol(-1)的结合能。在极性较高的溶剂如乙腈或丙酮中，结合常数低于5 M(-1)，这突出了3-AMP衍生物作为β-折叠模板的效用有限。电化学测量证实了各种Fc-二肽与3-TFAc-AMP之间的弱相互作用。Fc部分氧化还原电位的典型变化范围为0-20 mV。尝试通过碳二亚胺与氨基酸衍生物偶联在3-位修饰3-AMP，从而增强与Fc-肽的结合，得到了2-氨基酸取代的3-AMP衍生物。在2-位的取代阻断了结合位点，未观察到与Fc-二肽的相互作用。
