Bârzu T, Desmoulière A, Herbert J M, Level M, Herault J P, Petitou M, Lormeau J C, Gabbiani G, Pascal M
Centre Choay, Gentilly, France.
Eur J Pharmacol. 1992 Aug 25;219(2):225-33. doi: 10.1016/0014-2999(92)90300-s.
Selectively O-acylated derivatives of various glycosaminoglycans were prepared and tested in vitro for their anticoagulant activity and their antiproliferative effect on rat and rabbit smooth muscle cells. When O-acylation (butyrylation or hexanoylation) had been performed on periodate-depolymerized heparin fragments having very low anticoagulant activity, the antiproliferative potency was markedly increased (IC50 = 2 and 1 micrograms/ml respectively, versus 31 micrograms/ml for starting compound) without an increase in anticoagulant activity. The antiproliferative activity was related to the degree of acylation. The O-acylated derivatives of heparin fragments were also very active in reversing the de-differentiation of smooth muscle cell in culture, as estimated by the increase in the expression of alpha-smooth muscle actin and alpha-smooth muscle actin mRNA.
制备了各种糖胺聚糖的选择性O-酰化衍生物，并在体外测试了它们的抗凝血活性以及对大鼠和兔平滑肌细胞的抗增殖作用。当对具有非常低抗凝血活性的高碘酸盐解聚肝素片段进行O-酰化（丁酰化或己酰化）时，抗增殖效力显著提高（IC50分别为2和1微克/毫升，起始化合物为31微克/毫升），而抗凝血活性没有增加。抗增殖活性与酰化程度有关。通过α-平滑肌肌动蛋白和α-平滑肌肌动蛋白mRNA表达的增加来估计，肝素片段的O-酰化衍生物在逆转培养的平滑肌细胞去分化方面也非常活跃。
