Bellia Francesco, Amorini Angela Maria, La Mendola Diego, Vecchio Graziella, Tavazzi Barbara, Giardina Bruno, Di Pietro Valentina, Lazzarino Giuseppe, Rizzarelli Enrico
Department of Chemical Sciences, University of Catania, Viale A. Doria 6, 95125 Catania, Italy.
Eur J Med Chem. 2008 Feb;43(2):373-80. doi: 10.1016/j.ejmech.2007.03.038. Epub 2007 Apr 24.
Synthesis, antioxidant properties and resistance to carnosinase hydrolysis of histidine-containing dipeptides are reported in this study. Carnosine (beta-alanyl-l-histidine), homocarnosine (gamma-aminobutyryl-l-histidine) and anserine (beta-alanyl-3-methyl-l-histidine) were covalently derivatized with beta-cyclodextrin to form different OH- or NH-bound conjugates. Mass spectroscopic and (1)H NMR data were used to determine the structure and the purity of the various beta-cyclodextrin derivatives. The inhibitory effect towards oxidation of human LDL induced by Cu(2+) ions, was estimated by measuring malondialdehyde formation as a function of increasing concentrations of these newly synthesized compounds (the beta-cyclodextrin-anserine conjugated in 3 had the highest antioxidant effect). All derivatives had higher antioxidant effects than those of the corresponding free histidine-containing dipeptides. Resistance to rat brain carnosinase hydrolysis of the most active derivatives indicated that these compounds are good candidates for further studies in more complex cellular and animal models. Their possible applications for remedies in neurodegenerative disorders, such as Alzheimer's and Parkinson's diseases, are discussed.
本研究报道了含组氨酸二肽的合成、抗氧化特性及对肌肽酶水解的抗性。肌肽（β-丙氨酰-L-组氨酸）、高肌肽（γ-氨基丁酰-L-组氨酸）和鹅肌肽（β-丙氨酰-3-甲基-L-组氨酸）与β-环糊精共价衍生化，形成不同的OH-或NH-键合共轭物。利用质谱和（1）H NMR数据确定各种β-环糊精衍生物的结构和纯度。通过测量丙二醛的形成作为这些新合成化合物浓度增加的函数，评估了对Cu(2+)离子诱导的人低密度脂蛋白氧化的抑制作用（3中β-环糊精-鹅肌肽共轭物具有最高的抗氧化效果）。所有衍生物的抗氧化效果均高于相应的游离含组氨酸二肽。对最具活性衍生物的大鼠脑肌肽酶水解抗性表明，这些化合物是在更复杂的细胞和动物模型中进一步研究的良好候选物。讨论了它们在神经退行性疾病如阿尔茨海默病和帕金森病治疗中的可能应用。
