【摘要】：聚乙二醇(PEG)修飾是延長(zhǎng)蛋白藥物體內(nèi)半衰期和降低免疫原性的有效途徑。經(jīng)過(guò)單因素實(shí)驗(yàn),探索了PEG對(duì)LL-37與干擾素(IFN)-α2a融合蛋白修飾的最佳工藝條件,分別為:PEG分子量為5 000、融合蛋白濃度為0.6mg/mL、蛋白與PEG5000的物質(zhì)的量之比為1∶10、反應(yīng)溫度為4℃、反應(yīng)時(shí)間為4h、pH為9.0。經(jīng)正交實(shí)驗(yàn)表明,3個(gè)主要因素對(duì)蛋白修飾率的影響順序?yàn)槿诤系鞍诐舛鹊鞍譵PEG5000-SS的物質(zhì)量之比pH,最佳工藝條件為融合蛋白濃度為0.6mg/mL、蛋白與mPEG5000-SS的物質(zhì)的量之比為1∶10、pH為8.8。在最佳修飾條件下,三次平行實(shí)驗(yàn)的平均蛋白修飾率為86.98%。在最佳修飾條件下,蛋白的修飾率可穩(wěn)定達(dá)到85%以上,LL-37與IFN-α2a融合蛋白的干擾素活性保持率為58%以上,抗菌活性的保持率可達(dá)到97%以上。
[Abstract]:Polyethylene glycol (PEG) modification is an effective way to prolong the half-life and reduce the immunogenicity of protein drugs. The optimum modification conditions of LL-37 and interferon (IFN)-偽 2a fusion protein by PEG were investigated by single factor experiment. The molecular weight of PEG was 5 000, and the concentration of fusion protein was 0.6 mg / mL, respectively. The ratio of protein to PEG5000 is 1: 10, reaction temperature is 4 鈩，

本文編號(hào)：2413237