Wieczorek Z, Słoń J J, Siemion I Z
Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland.
Arch Immunol Ther Exp (Warsz). 1996;44(4):209-14.
Continuing our research on the immunomodulatory activity of the peptides related to the proteins of TGF-beta family, we have synthesized and investigated by Jerne's plaque forming cell (PFC) test and delayed type hypersensitivity (DTH) test the following linear peptides and their cyclic (disulphide-bridged) analogues: Lys-Thr-Pro-Lys-Ile (Ia) and Cys-Lys-Thr-Pro-Lys-Ile-Cys (Ib), Tyr-Ile-Gly-Lys-Thr-Pro (IIIa) and Cys-Tyr-Ile-Gly-Lys-Thr-Pro-Cys (IIIb), Tyr-Ile-Gly-Lys-Thr-Pro-Lys-Ile (IVa) and Cys-Tyr-Ile-Gly-Lys-Thr-Pro-Lys-Ile-Cys (IVb), Tyr-Tyr-Ile-Gly-Lys-Thr-Pro-Lys-Ile-Glu (Va) and Cys-Tyr-Tyr-Ile-Gly-Lys-Thr-Pro-Lys-Ile-Glu-Cys (Vb). It has been found that the insertion of the sequence of Ia into the disulphide bridged Ib generates a product with enhanced immunosuppressive activity. The similar procedure applied to IIIa, IVa and Va produces cyclic peptides devoid of any activity or of a diminished activity in DTH test. The exchange of Pro residue of Ia D-Pro resulted in the analogue IIa with a preserved immunosuppressive activity. The disulphide-bridged peptide IIb, a cyclic analogue of IIa, exhibited the same activity as IIa in both: PFC and DTH tests.
在继续我们对与转化生长因子-β家族蛋白质相关的肽的免疫调节活性的研究中，我们合成了以下线性肽及其环化（二硫键桥连）类似物，并通过耶尔恩氏空斑形成细胞（PFC）试验和迟发型超敏反应（DTH）试验进行了研究：赖氨酸-苏氨酸-脯氨酸-赖氨酸-异亮氨酸（Ia）和半胱氨酸-赖氨酸-苏氨酸-脯氨酸-赖氨酸-异亮氨酸-半胱氨酸（Ib）、酪氨酸-异亮氨酸-甘氨酸-赖氨酸-苏氨酸-脯氨酸（IIIa）和半胱氨酸-酪氨酸-异亮氨酸-甘氨酸-赖氨酸-苏氨酸-脯氨酸-半胱氨酸（IIIb）、酪氨酸-异亮氨酸-甘氨酸-赖氨酸-苏氨酸-脯氨酸-赖氨酸-异亮氨酸（IVa）和半胱氨酸-酪氨酸-异亮氨酸-甘氨酸-赖氨酸-苏氨酸-脯氨酸-赖氨酸-异亮氨酸-半胱氨酸（IVb）、酪氨酸-酪氨酸-异亮氨酸-甘氨酸-赖氨酸-苏氨酸-脯氨酸-赖氨酸-异亮氨酸-谷氨酸（Va）和半胱氨酸-酪氨酸-酪氨酸-异亮氨酸-甘氨酸-赖氨酸-苏氨酸-脯氨酸-赖氨酸-异亮氨酸-谷氨酸-半胱氨酸（Vb）。已发现将Ia的序列插入二硫键桥连的Ib中会产生一种具有增强免疫抑制活性的产物。应用于IIIa、IVa和Va的类似程序产生的环肽在DTH试验中无任何活性或活性降低。将Ia的脯氨酸残基替换为D-脯氨酸得到具有保留免疫抑制活性的类似物IIa。二硫键桥连的肽IIb，即IIa的环化类似物，在PFC试验和DTH试验中均表现出与IIa相同的活性。
