【摘要】：細(xì)胞外基質(zhì)中的粘附糖蛋白在細(xì)胞粘附中起重要作用,RGD三肽是許多粘附蛋白所共有的細(xì)胞間識別的最小序列,這一序列在介導(dǎo)細(xì)胞粘附、遷移和生長方面起重要作用。目前關(guān)于RGD的研究主要集中在RGD肽對血小板功能的影響、RGD肽在抗栓藥物中的應(yīng)用、RGD肽在骨組織的誘導(dǎo)再生中的研究、RGD肽在腫瘤轉(zhuǎn)移和新生血管中的研究以及腫瘤靶向治療中的應(yīng)用。 在本文中,我們主要討論了RGD三肽前體Bz-RGD-OMe的合成反應(yīng),這是個在動力學(xué)控制下的酶促肽合成反應(yīng)。首先,合成Bz-RG-OEt,這是在胰蛋白酶催化、有機溶劑水共混體系下進行的,反應(yīng)的最佳條件為:pH 8.0, 30℃,乙醇/ This-HCl緩沖液(85:15, V/V),�；w與親核試劑的摩爾比為1:5,Bz-Arg-OEt 0.05mM。二肽的產(chǎn)率為70.6%。然后,合成Bz-RGD-OMe,這是個木瓜蛋白酶催化的可溶性三肽前體在水相介質(zhì)中進行的合成反應(yīng)。反應(yīng)的最佳條件為:pH8.1,40℃,KCl水溶液反應(yīng)體系(含有8mM EDTA和2mM DTT),底物Bz-RG(-OEt)和D(-OMe)2?HCl分別為0.05M和0.15M,反應(yīng)時間為60min,最大轉(zhuǎn)化率為62.41%。此外,還采用傳統(tǒng)的液相化學(xué)法合成了游離RGD三肽。在論文的后部分,我們對RGD-聚乳酸微球的制備進行了初步探討,并采用正交試驗設(shè)計優(yōu)化了試驗條件,最后得到最優(yōu)包封率為83.124%。
[Abstract]:Adhesion glycoproteins in extracellular matrix play an important role in cell adhesion. RGD tripeptide is the least recognized sequence common to many adhesion proteins, which plays an important role in mediating cell adhesion, migration and growth. At present, the research on RGD mainly focuses on the effect of RGD peptide on platelet function, the application of RGD peptide in antithrombotic drugs, and the study of RGD peptide in the induction and regeneration of bone tissue. The study of RGD peptide in tumor metastasis and neovascularization and the application of tumor targeting therapy. In this paper, we mainly discuss the synthesis of RGD tripeptide precursor Bz-RGD-OMe, which is an enzymatic peptide synthesis reaction controlled by kinetics. First, the synthesis of Bz-RG-OEt, was carried out in a trypsin-catalyzed, organic solvent-water blend system. The optimum reaction conditions were as follows: pH 8.0, 30 鈩，

本文編號：2468785