發(fā)布時(shí)間：2018-04-15 21:34

  本文選題：蛋白質(zhì)化學(xué)合成 + 自然化學(xué)連接　； 參考：《合肥工業(yè)大學(xué)》2017年碩士論文

【摘要】：隨著人類基因組計(jì)劃的完結(jié),蛋白質(zhì)結(jié)構(gòu)與功能的關(guān)系成為當(dāng)前生物學(xué)研究的熱點(diǎn)。其中,蛋白質(zhì)的翻譯后修飾受到科研人員的廣泛關(guān)注(如甲基化,磷酸化,泛素化和類泛素化等)。這些翻譯后修飾蛋白在生物體內(nèi)發(fā)揮著重要的生理功能。SUMO蛋白是一種類泛素蛋白,它可以通過E1,E2,E3三級(jí)酶聯(lián)反應(yīng)共價(jià)偶聯(lián)到某些底物蛋白上,形成SUMO修飾的目標(biāo)蛋白,而SUMO化蛋白在生物體內(nèi)的核質(zhì)轉(zhuǎn)運(yùn)、信號(hào)傳導(dǎo)、DNA的損傷修復(fù)和蛋白質(zhì)的降解等過程中發(fā)揮著重要的作用。在SUMO化的過程中,SUMO蛋白本身也可以被乙�；�或者多聚化,SUMO蛋白本身的這種修飾對(duì)SUMO化蛋白的功能發(fā)揮同樣具有重要的作用。為了對(duì)乙�；疭UMO和多聚SUMO蛋白在SUMO化修飾過程中的功能作進(jìn)一步研究,獲得性質(zhì)均一的乙酰化SUMO和多聚SUMO蛋白是相關(guān)研究得以進(jìn)行的關(guān)鍵。由于傳統(tǒng)生物表達(dá)的方法只能獲得由天然氨基酸組成的蛋白質(zhì),而類似乙酰化或者多聚化這種翻譯后修飾蛋白往往很難獲得。蛋白質(zhì)化學(xué)合成技術(shù)憑借其能夠在原子尺度精準(zhǔn)構(gòu)筑蛋白質(zhì)的優(yōu)勢(shì),是獲得這些翻譯后修飾蛋白非常有效的一種手段。其中,Liu課題組將酰肼作為C端硫酯的掩蔽基團(tuán),簡(jiǎn)化了肽片段連接中C端硫酯的合成問題,具有操作簡(jiǎn)單,效率高的優(yōu)點(diǎn)。本文作者運(yùn)用基于多肽酰肼連接的蛋白質(zhì)化學(xué)合成策略應(yīng)用于SUMO-2蛋白,乙酰化SUMO蛋白,D型SUMO蛋白和二聚SUMO蛋白的化學(xué)合成中,實(shí)現(xiàn)了兩片段SUMO-2,乙�；疭UMO-2,D型SUMO以及四片段二聚SUMO蛋白的化學(xué)全合成,并通過生化實(shí)驗(yàn)驗(yàn)證了合成蛋白的正確性。本工作為進(jìn)一步化學(xué)合成的多聚泛素、多聚類泛素蛋白提供了一種普適性方法,進(jìn)而闡明蛋白質(zhì)類泛素化特異性合成、識(shí)別、降解過程的生物化學(xué)機(jī)制的研究提供了有效的工具。
[Abstract]:With the completion of the Human Genome Project, the relationship between protein structure and function has become a hot topic in biological research.Among them, post-translational modification of proteins has attracted extensive attention (such as methylation, phosphorylation, ubiquitin and ubiquitin).These posttranslational modified proteins play an important physiological function in vivo. Sumo protein is a Ubiquitin protein, which can be covalently coupled to some substrate proteins by E1OE2E3 tertiary enzyme-linked reaction to form the target protein modified by SUMO.However, SUMO proteins play an important role in the processes of nuclear and cytoplasmic transport, signal transduction, damage repair and protein degradation.In the process of SUMO, Sumo protein itself can also be modified by acetylation or polymerylation. This modification also plays an important role in the function of SUMO protein.In order to further study the functions of acetylated SUMO and poly (SUMO) proteins in the process of SUMO modification, uniform acetylated SUMO and poly (SUMO) proteins are the key to the study.Because traditional biological expression methods can only obtain proteins composed of natural amino acids, post-translational modified proteins such as acetylation or polymerization are often difficult to obtain.Protein chemosynthesis is an effective way to obtain these post-translational modified proteins because of its advantage of precisely constructing proteins on atomic scale.Liu group used hydrazide as the masking group of C-terminal thioester, which simplifies the synthesis of C-terminal thioester in peptide fragment connection, and has the advantages of simple operation and high efficiency.In this paper, the authors used the protein chemical synthesis strategy based on polypeptide hydrazide binding in the chemical synthesis of SUMO-2 protein, acetylated SUMO protein D type SUMO protein and dimer SUMO protein.The chemical synthesis of two fragments SUMO-2, acetylated SUMO-2 D type SUMO and four fragments dimeric SUMO protein was realized, and the correctness of the synthesized protein was verified by biochemical experiments.This work provides a universal method for the further chemical synthesis of polyubiquitin, polyubiquitin protein, and further elucidates the specific synthesis and recognition of protein ubiquitin.The study of biochemistry mechanism of degradation process provides an effective tool.
【學(xué)位授予單位】：合肥工業(yè)大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：O629.73

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 陳晨晨;李思踐;陳軼群;許華建;李宜明;;多肽酰肼法合成Nesiritide[J];有機(jī)化學(xué);2014年07期

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本文編號(hào)：1755892