Thierry J, Papet M P, Saez-Servent N, Plissonneau-Haumont J, Potier P, Lenfant M
Institut de Chimie des Substances Naturelles, CNRS 91198 Gif-sur-Yvette, France.
J Med Chem. 1990 Aug;33(8):2122-7. doi: 10.1021/jm00170a012.
Analogues of NAcSerAspLysPro (AcSDKP), a natural regulator of hematopoiesis isolated from fetal calf bone marrow, were synthesized. The biological activity of these molecules were evaluated in vitro in the rosette assay, which measures the interaction between human Jurkat T-cells and sheep red blood cells. In this test, the tripeptide SerAspLys was the most efficient. Inhibitory activity was detected at the concentration 10(-14) M for the analogue and at 10(-9) M for the parent tetrapeptide. The dipeptide NAcSerAsp still showed activity but at much higher doses (10(-6) M). Substitution of polar amino acids led mostly to inactive molecules. Thus, replacement of Ser by Ala, or Lys by Orn yielded completely inactive compounds and replacement of Asp by Glu decreased the activity (10(-6) M). The present study gives an insight into the role of individual amino acids of AcSDKP in the inhibition of the rosette formation which implicates interactions with T-cell CD2 glycoprotein.
从胎牛骨髓中分离出的一种天然造血调节剂——NAcSerAspLysPro（AcSDKP）的类似物被合成出来。这些分子的生物活性在体外通过玫瑰花结试验进行评估，该试验用于测量人类Jurkat T细胞与绵羊红细胞之间的相互作用。在这个试验中，三肽SerAspLys最为有效。该类似物在浓度为10^(-14) M时检测到抑制活性，而母体四肽在10^(-9) M时检测到抑制活性。二肽NAcSerAsp仍显示出活性，但剂量要高得多（10^(-6) M）。极性氨基酸的取代大多导致分子无活性。因此，用Ala取代Ser，或用Orn取代Lys会产生完全无活性的化合物，用Glu取代Asp会降低活性（10^(-6) M）。本研究深入探讨了AcSDKP中单个氨基酸在抑制玫瑰花结形成中的作用，这涉及与T细胞CD2糖蛋白的相互作用。
