Zubrzak Paweł, Banaś Agnieszka, Kaczmarek Krzysztof, Leplawy Mirosław T, Sochacki Marek, Kowalski Marek L, Szkudlińska Barbara, Zabrocki Janusz, Di Lello Paola, Isernia Carla, Saviano Michele, Pedone Carlo, Benedetti Ettore
Institute of Organic Chemistry, Technical University of Łódź, Zeromskiego 116, 90-924 Łódź,Poland.
Biopolymers. 2005;80(2-3):347-56. doi: 10.1002/bip.20182.
Linear and cyclic cyclolinopeptide A (CLA) analogues containing alpha-hydroxymethylleucine (HmL) in positions 1, 4, and 1&4, and alpha-hydroxymethylvaline (HmV) in position 5, were synthesized by the solid-phase peptide strategy and cyclized with the 1-Ethyl-3-(3-dimethylaminopropyl)-carbodiimide/1-hydroxy-7-azabenzotriazole (EDC/HOAt) reagent. The peptides were examined for their immunosuppressive activity in the lymphocyte proliferation assays (LPA). Only HmL-containing peptides demonstrated at about 25% lower immunosuppressive activity, but they are four times more soluble in water solutions than the native CLA. It seems from the LPA results that peptide [(HmL4)CLA] is the most promising for further studies. This peptide was characterized in solution, at room temperature in CDCl3, and the conformation compared with that observed for CLA in the solid state.
通过固相肽策略合成了在第1、4和1&4位含有α-羟甲基亮氨酸（HmL）且在第5位含有α-羟甲基缬氨酸（HmV）的线性和环状环脂肽A（CLA）类似物，并用1-乙基-3-(3-二甲基氨基丙基)-碳二亚胺/1-羟基-7-氮杂苯并三唑（EDC/HOAt）试剂进行环化。在淋巴细胞增殖试验（LPA）中检测了这些肽的免疫抑制活性。只有含HmL的肽表现出约低25%的免疫抑制活性，但它们在水溶液中的溶解度是天然CLA的四倍。从LPA结果来看，肽[(HmL4)CLA]最有希望用于进一步研究。在室温下于CDCl₃中对该肽进行了溶液表征，并将其构象与固态CLA的构象进行了比较。
