IMMUNOAFFINITY ADSORPTION METHODS FOR TAXOL

研究了分离毫克级抗- 抗癌药物紫杉醇从密切相关的类似物通过免疫亲和 在I期研究中证实了色谱法（IAC）。 在 该技术可用于紫杉醇样品的分析 在HPLC或HPLC-MS分析之前制备。其他IAC系统，使用 不同的抗紫杉烷单克隆抗体，现在可以研究分离其他 紫杉醇同系物和代谢物。HBG已经有可用的mAb， 浆果赤霉素III特异性和紫杉烷类特异性。IAC方法结合 这些单克隆抗体可用于基础和临床研究 问题，如临床药代动力学， 替代供应来源，以及分离新的同系物， 代谢物。 分子生物学技术的发展使紫杉醇的大规模应用成为可能 将IAC方法用于制备规模。克隆低分子量 抗体片段可以在微生物培养物中表达， 规模隔离程序。这些碎片，体积小于 完整免疫球蛋白，应允许提高柱容量和流量 速率，同时保持所需的选择性。克隆程序还 提供辅助研究所需的遗传信息，例如 融合蛋白的构建，小分子肽 模拟物和序列/活性研究。

The technical feasibility of separating milligram amounts of the anti- cancer drug taxol from closely related analogs by immunoaffinity chromatography (IAC) was demonstrated in Phase I research. At the analytical scale, this technique may be useful for taxol sample preparation prior to HPLC or HPLC-MS analysis. Other IAC systems, using different anti-taxane mAbs, can now be investigated for isolation of other taxol congeners and metabolites. HBG already has available mAbs which are baccatin III-specific and taxane-class specific. IAC methods incorporating these mAbs may be applied to the study of basic and clinical research questions, such as clinical pharmacokinetics, identification of alternative supply sources, and isolation of new congeners and metabolites. The techniques of molecular biology make possible the extension of taxol IAC methodology to the preparative scale. Cloned low molecular weight antibody fragments can be expressed in microbial culture for use in large- scale isolation procedures. These fragments, which are less bulky than whole immunoglobulin, should permit improved column capacity and flow rate, while retaining the desired selectivity. The cloning procedures also provide the genetic information necessary for ancillary studies, such as the construction of fusion proteins, low molecular weight peptide mimetics, and sequence/activity studies.