RESOLUTION OF FLURBIPROFEN BY AN ENTRAPPED LIPASE

长期目标是酶或活细胞的应用。 在多糖珠中。一个文学例子是困住小岛的 朗格汉斯，它可以表现为一个生物人工胰腺。初步研究 这些努力将使研究人员熟悉体外动力学 有机介质中对映体的拆分。脂肪酶尤其具有 证明在酯化反应中反应速度更快，对映体选择性更好 有机介质中的酯交换反应优于水介质中的酯交换反应。这个 拟议的研究还包括在珠子中加入脂肪酶。 以便于酶的回收和随后的输送。短期内 目标是拆分具有药理活性的对映体。 使用对映体选择性的抗炎药氟比洛芬 通过包裹在多糖基质中的脂肪酶进行的酯化反应。 分离活性对映体无疑将是一种调节 需求，因为只管理活动的 对映体可以降低毒性和剂量。有明显的优势 包括快速的对映选择性反应的这种方法的；重复的 酶可回收后的应用：终端拆分 合成序列，这是经济的。 在第一年，将通过评估来优化溶剂和脂肪酶 哪种组合提供最快的反应、最大的产率和 对映体选择性最高。第二年，多糖凝胶 珠子是用来包埋脂肪酶的。成功的聚合物将 提供坚固的球形基质，可以保留酶，最大限度地减少 干扰活性，并允许底物和产品扩散。这个 珠子的透气性将通过测量基材进行调查 在多糖基质中的扩散性。反应的动力学参数 将包埋的酶与第三种游离酶进行比较 年。一个效率因子将测量包埋到游离酶的 活动。小球的稳定性、催化活性和酶 保留率将作为重复应用的函数进行评估。

The long-term goals are applications of enzymes or viable cells entrapped in polysaccharide beads. A literature example is entrapped islets of Langerhans which can behave as a bioartificial-pancreas. Initial research efforts will familiarize the investigator with the ex vivo kinetic resolution of enantiomers in organic media. Lipases in particular have proved to be faster and more enantioselective in esterification and transesterification reactions in organic media than in aqueous media. The proposed research also includes the incorporation of a lipase into beads for easy recovery and subsequent delivery of the enzyme. The short term goal is the resolution of the pharmacologically active enantiomer from an anti-inflammatory agent, flurbiprofen, by employing enantioselective esterification by the lipase entrapped within a polysaccharide matrix. Isolation of the active enantiomer will undoubtedly be a regulatory requirement in the near future because administering only the active enantiomer can reduce the toxicity and dose. There are distinct advantages to this method including a rapid, enantioselective reaction; repeated applications since the enzyme can be recovered: and terminal resolution in the synthesis sequence, which is economical. In the first year, the solvent and lipase will be optimized by evaluating which combination provides the fastest reaction, the greatest yield, and the highest enantioselectivity. In the second year, polysaccharide gel beads are fabricated to entrap the lipase. The successful polymer will provide a rugged, spherical matrix which can retain the enzyme, minimize interference with activity, and allow substrate and product diffusion. The permeability of the bead will be investigated by measuring the substrate diffusivity within the polysaccharide matrix. Kinetic parameters of the entrapped enzyme will be compared to those of the free enzyme in the third year. An efficiency factor will measure the entrapped to free enzyme activity. The stability of the bead, catalytic activity and enzyme retention will be evaluated as a function of repeated applications.