過氧化物酶肽類模擬物的設(shè)計、合成及酶學(xué)性質(zhì)表征
發(fā)布時間:2018-01-01 06:39
本文關(guān)鍵詞:過氧化物酶肽類模擬物的設(shè)計、合成及酶學(xué)性質(zhì)表征 出處:《吉林大學(xué)》2006年碩士論文 論文類型:學(xué)位論文
【摘要】:過氧化物酶對多種由于自由基損傷而引的疾病的預(yù)防和治療有著重要意義,但由于天然過氧化物酶作為抗氧化藥物的種種缺點(diǎn),用模擬酶的辦法來制備具有藥用價值的過氧化物酶的模擬物成為了新的研究方向。本論文以過氧化物酶的輔基亞血紅素為篩選靶目標(biāo),通過噬菌體表面展示肽庫篩選出一系列的與亞血紅素特異性結(jié)合的短肽配基,并得到了保守序列。以得到的序列為基礎(chǔ),設(shè)計合成了一系列的含有His和Arg的亞血紅素—七肽化合物模擬酶,活性達(dá)到了天然微過氧化物酶MP-11活力的90%以上,其中DhHP-2RⅠ( Dh-AlaHisArgAlaAlaArg)的催化效率最高。對缺少His但包含Arg殘基的序列進(jìn)行了二級結(jié)構(gòu)預(yù)測,根據(jù)預(yù)測結(jié)果合成了亞血紅素—十二肽化合物模擬酶,其活性達(dá)到了天然微過氧化物酶MP-11活力的50%以上。以上的工作使我們進(jìn)一步確定了Arg是參與過氧化物酶活性中心的重要氨基酸,為今后設(shè)計活性更高的過氧化物模擬酶打下了基礎(chǔ)。
[Abstract]:Peroxidase is of great significance to the prevention and treatment of many diseases caused by free radical damage, but it has a variety of shortcomings as antioxidant drugs. The preparation of peroxidase mimics with medicinal value has become a new research direction. In this paper, coheme of peroxidase was selected as the target target. A series of short peptide ligands with specific binding to heme were screened by phage display peptide library, and conserved sequences were obtained based on the obtained sequences. A series of heme-heptapeptide mimic enzymes containing His and Arg were designed and synthesized. The activities of these mimetic enzymes reached over 90% of the MP-11 activity of natural microperoxidase. The catalytic efficiency of DhHP-2R 鈪,
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