Buchli P, Ciardelli T
Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, New Hampshire 03755-3833.
Arch Biochem Biophys. 1993 Dec;307(2):411-5. doi: 10.1006/abbi.1993.1608.
Point mutations at position 141 in the murine interleukin-2 (IL-2) sequence have been reported to generate proteins with full antagonist activity on some IL-2-dependent cell lines. To evaluate the potential therapeutic utility of this observation, we have prepared recombinant human IL-2 with a point mutation at the corresponding position (Asp for Gln 126) and examined its structural and biologic properties. This mutation apparently induces minor changes in tertiary conformation accompanied by an increased sensitivity to changes in pH. The biologic activity of this analog is greatly reduced, primarily as a result of decreased affinity to the beta/gamma IL-2 receptor complex; however, it is only weakly antagonistic to the IL-2 response of normal peripheral blood lymphocytes.
据报道，小鼠白细胞介素-2（IL-2）序列中第141位的点突变可产生对某些IL-2依赖细胞系具有完全拮抗活性的蛋白质。为了评估这一观察结果的潜在治疗用途，我们制备了在相应位置（第126位谷氨酰胺突变为天冬氨酸）具有点突变的重组人IL-2，并检测了其结构和生物学特性。这种突变显然引起三级构象的微小变化，同时伴随着对pH值变化敏感性的增加。该类似物的生物学活性大大降低，主要是由于对β/γ IL-2受体复合物的亲和力下降；然而，它对正常外周血淋巴细胞的IL-2反应仅有微弱的拮抗作用。
