Je Jae-Young, Park Pyo-Jam, Kim Bokyung, Kim Se-Kwon
Department of Chemistry, Pukyong National University, Busan 608-737, Korea.
Biopolymers. 2006 Oct 15;83(3):250-4. doi: 10.1002/bip.20553.
To develop angiotensin I converting enzyme (ACE) inhibitory chitin derivatives based on the properties of ACE inhibitors, chitins with different degree of deacetylation were chemically modified by grafting 2-chloroethylamino hydrochloride onto chitin at the C-6 position. Three kinds of chitin derivatives were prepared and designated as aminoethyl-chitin (AEC) with 10% degree of deacetylation, aminoethyl-chitin with 50% degree of deacetylation (AEC50), and aminoethyl-chitin with 90% degree of deacetylation (AEC90). IC50 values of three chitin derivatives on ACE were 0.064 microM (AEC), 0.038 microM (AEC50), and 0.103 microM (AEC90). The results of Dixon plots revealed that AEC50 was a competitive inhibitor, and the inhibition constant (Ki) value was 0.021 microM. In addition, the antihypertensive effect of AEC50 on spontaneously hypertensive rats (SHR) was evaluated, and the result showed that it effectively decreased systolic blood pressure (SBP) in a dose-dependent manner.
为了基于血管紧张素I转换酶（ACE）抑制剂的特性开发具有ACE抑制活性的几丁质衍生物，通过将2-氯乙胺盐酸盐接枝到不同脱乙酰度几丁质的C-6位进行化学修饰。制备了三种几丁质衍生物，分别命名为脱乙酰度为10%的氨乙基几丁质（AEC）、脱乙酰度为50%的氨乙基几丁质（AEC50）和脱乙酰度为90%的氨乙基几丁质（AEC90）。三种几丁质衍生物对ACE的IC50值分别为0.064微摩尔（AEC）、0.038微摩尔（AEC50）和0.103微摩尔（AEC90）。Dixon图结果显示AEC50是一种竞争性抑制剂，抑制常数（Ki）值为0.021微摩尔。此外，评估了AEC50对自发性高血压大鼠（SHR）的降压作用，结果表明它能有效降低收缩压（SBP），且呈剂量依赖性。
