Andrulis I L, Evans-Blackler S, Siminovitch L
J Biol Chem. 1985 Jun 25;260(12):7523-7.
The amino acid analog, albizziin, which acts as a competitive inhibitor of asparagine synthetase with respect to glutamine was used to isolate mutants of Chinese hamster ovary cells with alterations in levels of the target enzyme. These mutant lines have been characterized biochemically and genetically. Mutants selected in a single step are up to 40-fold more resistant to the drug than the parental line, express levels of asparagine synthetase activity 6-17-fold greater than that of wild type cells, and act co-dominantly in hybrids. Several classes of mutations can be distinguished on the basis of cross-resistance to beta-aspartyl hydroxamate, another amino acid analog. Studies on asparagine synthetase indicate that resistance to albizziin may be due to altered regulation of asparagine synthetase, structural mutations of the enzyme, and gene amplification.
氨基酸类似物合欢氨酸是谷氨酰胺的天冬酰胺合成酶竞争性抑制剂，利用它来分离靶酶水平发生改变的中国仓鼠卵巢细胞突变体。这些突变株已在生物化学和遗传学方面得到鉴定。一步筛选出的突变体对该药物的抗性比亲代细胞株高40倍，天冬酰胺合成酶活性水平比野生型细胞高6至17倍，并且在杂种细胞中呈共显性。根据对另一种氨基酸类似物β-天冬氨酰异羟肟酸的交叉抗性可区分出几类突变。对天冬酰胺合成酶的研究表明，对合欢氨酸的抗性可能是由于天冬酰胺合成酶调控改变、该酶的结构突变以及基因扩增所致。
