Design and Functional Evaluation of Albumin Mutants for Improving Medicinal Efficacy

点击翻译按钮获取中文摘要

This investigation was undertaken to develop a safe and effective albumin using site-directed mutagenesis techniques. The results obtained in this study are as follow :1) Two single-mutants (K199A, K525A) were produced. The recombinant albumins were correctly folded, as evidenced by the fact that they showed similar patterns as the native albumin in the far- and near-UV CD spectrum as well as reactivity towards polyclonal anti-serum raised against native albumin.2) Thermal denaturation experiments by using GdnCl and DSC revealed no significant difference in conformational stability for native and mutant albumins.3) The ligand binding properties and esterase-like activity of the albumin mutants were nearly the same as those for the native albumin.4) The plasma levels of the albumin mutants labeled with ^<125>I after intravenous bolus injections to rats showed two-phase profiles but their half-lives were shorten than that for the native albumin.From the above results, there are potentials for the design of such albumin mutants but further investigations need to be carried out in order to serve the objectives of better safety and efficacy of albumin preparation.