Doukas M, Chavan A, Gass C, Nickel P, Boone T, Haley B
Veterans Affairs Medical Center, Lexington, Kentucky 40536-0093, USA.
Cancer Res. 1995 Nov 15;55(22):5161-3.
Suramin and suramin analogues strongly inhibit both nucleotide interaction with the nucleotide-binding site of granulocyte-macrophage colony-stimulating factor (GM-CSF) and bioactivity of the molecule as assessed by competition photoaffinity labeling and cell proliferation assay, respectively. The half-maximal inhibition of cell proliferation by suramin occurs at 68 +/- 2.5 microM; three suramin analogues achieved comparable activity. The degree of competitive inhibition of nucleotide-binding by these compounds and the inhibition of GM-CSF bioactivity are correlated such that the compounds show similar rank-order by both of these methods. The strong interaction of suramin and related compounds with the nucleotide-binding site may mimic nucleotide-mediated inhibition of GM-CSF bioactivity and may be an important mechanism by which suramin acts as a pharmacological anti-growth factor agent.
通过竞争光亲和标记和细胞增殖试验分别评估，苏拉明及其类似物强烈抑制核苷酸与粒细胞巨噬细胞集落刺激因子（GM-CSF）核苷酸结合位点的相互作用以及该分子的生物活性。苏拉明对细胞增殖的半数最大抑制浓度为68±2.5微摩尔；三种苏拉明类似物具有相当的活性。这些化合物对核苷酸结合的竞争抑制程度与GM-CSF生物活性的抑制相关，使得这些化合物在这两种方法中显示出相似的排序。苏拉明及相关化合物与核苷酸结合位点的强烈相互作用可能模拟了核苷酸介导的GM-CSF生物活性抑制，并且可能是苏拉明作为药理学抗生长因子药物发挥作用的重要机制。
