基于核Fisher判别分析的蛋白质氧链糖基化位点的预测

以各种窗口长度的蛋白质样本序列为研究对象,实验样本用稀疏编码方式编码,使用核Fisher判别分析(KFDA)的方法来预测蛋白质氧链糖基化位点。首先通过非线性映射(由核函数隐含定义)将样本映射到特征空间,然后在特征空间中用Fisher判别分析进行分类。进一步,用多数投票策略对各种窗口下的分类器进行组合以综合多个窗口的优势。实验结果表明,使用组合KFDA的方法预测的效果优于FDA和PCA以及单个KFDA分类器的预测效果,预测准确率为86.5%。     

Systematic Review: Drug Repositioning for Congenital Disorders of Glycosylation (CDG)

Advances in research have boosted therapy development for congenital disorders of glycosylation (CDG), a group of rare genetic disorders affecting protein and lipid glycosylation and glycosylphosphatidylinositol anchor biosynthesis. The (re)use of known drugs for novel medical purposes, known as drug repositioning, is growing for both common and rare disorders. The latest innovation concerns the rational search for repositioned molecules which also benefits from artificial intelligence (AI). Compared to traditional methods, drug repositioning accelerates the overall drug discovery process while saving costs. This is particularly valuable for rare diseases. AI tools have proven their worth in diagnosis, in disease classification and characterization, and ultimately in therapy discovery in rare diseases. The availability of biomarkers and reliable disease models is critical for research and development of new drugs, especially for rare and heterogeneous diseases such as CDG. This work reviews the literature related to repositioned drugs for CDG, discovered by serendipity or through a systemic approach. Recent advances in biomarkers and disease models are also outlined as well as stakeholders’ views on AI for therapy discovery in CDG.     

p-Coumaric acid,Kaempferol, Astragalin and Tiliroside Influence the Expression of Glycoforms in AGS Gastric Cancer Cells

Abnormal glycosylation of cancer cells is considered a key factor of carcinogenesis related to growth, proliferation, migration and invasion of tumor cells. Many plant-based polyphenolic compounds reveal potential anti-cancer properties effecting cellular signaling systems. Herein, we assessed the effects of phenolic acid, p-coumaric acid and flavonoids such as kaempferol, astragalin or tiliroside on expression of selected cancer-related glycoforms and enzymes involved in their formation in AGS gastric cancer cells. The cells were treated with 80 and 160 µM of the compounds. RT-PCR, Western blotting and ELISA tests were performed to determine the influence of polyphenolics on analyzed factors. All the examined compounds inhibited the expression of MUC1, ST6GalNAcT2 and FUT4 mRNAs. C1GalT1, St3Gal-IV and FUT4 proteins as well as MUC1 domain, Tn and sialyl T antigen detected in cell lysates were also lowered. Both concentrations of kaempferol, astragalin and tiliroside also suppressed ppGalNAcT2 and C1GalT1 mRNAs. MUC1 cytoplasmic domain, sialyl Tn, T antigens in cell lysates and sialyl T in culture medium were inhibited only by kaempferol and tiliroside. Nuclear factor NF-κB mRNA expression decreased after treatment with both concentrations of kaempferol, astragalin and tiliroside. NF-κB protein expression was inhibited by kaempferol and tiliroside. The results indicate the rationality of application of examined polyphenolics as potential preventive agents against gastric cancer development.     

食品加工中蛋白质的糖基化改性

蛋白质糖基化不仅存在于生物体自然过程中,也是改善蛋白质活性的一种新方法。以往的研究表明蛋白质与糖基化接枝能够显著改善蛋白质的功能特性且优于其他改性方法。文章系统阐述了蛋白质糖基化改性的反应机理、合成方法、评价指标,糖基化接枝对蛋白质的溶解性、乳化性、热稳定性、抗氧化性、溶菌性等特性的改善以及对蛋白质结构的影响,并对蛋白质糖基化改性的研究方向进行了展望。      

糖基化改性提高大豆分离蛋白凝胶特性的研究

研究蛋白-葡萄糖质量比（4∶1、2∶1、1∶1、1∶2）、反应温度（70、80、90℃）和反应时间（0、1、2、3、4、5、6 h）对大豆分离蛋白糖基化产物蛋白凝胶特性的影响。结果表明:反应体系的颜色随加热时间延长逐渐加深,p H逐渐降低;在适当的糖基化改性条件下,大豆分离蛋白（SPI）凝胶质构特性呈现先升高后下降的趋势,在蛋白与葡萄糖质量比为1∶1时,70℃下反应6 h所得产物的硬度最大值达383.21 g,是未改性SPI硬度的7.51倍;相同比例底物在70℃反应4 h所得产物的弹性最大,达到0.981,比天然SPI的弹性提高了8.16%;不同底物比例的各温度反应体系产物的色差值随着加热时间的增加均逐渐变大;SPI在SDS-PAGE图谱中主要显示了6条带,不同比例反应底物在70、80、90℃反应1⁶ h的糖基化产物均在大于200 k D分子量处出现新的条带。因此,对大豆分离蛋白进行适当的糖基化改性能够有效地提高其凝胶特性。      

Cloning and characterization of the Hansenula polymorpha homologue of the Saccharomyces cerevisiae MNN9 gene

A gene homologous to Saccharomyces cerevisiae MNN9 has been cloned and characterized in the methylotrophic yeast Hansenula polymorpha. This gene was cloned from a H. polymorpha genomic DNA library using the S. cerevisiae MNN9 gene as a probe. The H. polymorpha MNN9 homologue (HpMNN9) contained a 1062 bp open reading frame encoding a predicted protein of 354 amino acids. The deduced amino acid sequence showed 58% and 51% identity, respectively, with the S. cerevisiae and Candida albicans Mnn9 proteins. Disruption of HpMNN9 leads to phenotypic effects suggestive of cell wall defects, including detergent sensitivity and hygromycin B sensitivity. The hygromycin B sensitivity of S. cerevisiae mnn9 null mutant was complemented in the presence of the HpMNN9 gene. The DNA sequence of the H. polymorpha homologue has been submitted to GenBank with the Accession No. AF264786.     

Hypoglycaemic effect of comatin,an antidiabetic substance separated from Coprinus comatus broth,on alloxan-induced-diabetic rats

Comatin, an inhibitor of the non-enzymatic glycosylation (NEG) reaction, was isolated from Coprinus comatus fermentation broth by macroporous resin separation, followed by chromatographic purification using a C18 reversed-phase column. The compound was identified as 4,5-dihydroxy-2-methoxy-benzaldehyde by high-resolution MS, IR, NMR and UV analyses. The hypoglycaemic effect of comatin, on both normal and alloxan-induced-diabetic rats, was investigated in the paper. The blood glucose concentration of normal rats treated by the comatin at 80 mg/kg body weight was reduced from 5.14 mM to 4.28 mM in 3 h. Also, the concentrations of fructosamine, triglycerides and total cholesterol in induced-diabetic rats were significantly decreased. These results indicated that comatin could maintain a low level of blood glucose and improve glucose tolerance.     

乳清蛋白菊粉糖基化复合物的褐变特性与抗氧化活性

以褐变程度及抗氧化活性为检测指标,研究湿热反应条件对乳清蛋白菊粉糖基化复合物的褐变特性与抗氧化活性的影响。研究结果表明:反应物浓度越大,反应温度越高,乳清蛋白菊粉糖基化产物的褐变强度越大,抗氧化活性越强;起始反应pH值越大,乳清蛋白菊粉糖基化产物的褐变强度及还原能力越强,而其DPPH.清除能力呈现先升高后降低的趋势。当反应物浓度为6%,温度为100℃,起始反应pH值为9时,所获得的乳清蛋白糖基化产物抗氧化活性较强。     

糖基化反应条件对乳清蛋白——麦芽糖复合物抗原性的影响

研究了将麦芽糖通过糖基化引入到乳清蛋白制备乳清蛋白-麦芽糖,用间接竞争ELISA法测定不同反应时间不同质量比的乳清蛋白-麦芽糖中α-乳白蛋白和β-乳球蛋白的抗原性的变化。结果表明,糖基化能有效降低α-乳白蛋白和β-乳球蛋白的抗原性,α-乳白蛋白的抗原性可以从26.2 mg/L降低到14.4 mg/L,β-乳球蛋白的抗原性可以从95.1 mg/L降低到22.4 mg/L。反应时间对不同质量比的乳清蛋白-麦芽糖中α-乳白蛋白和β-乳球蛋白的抗原性有较大影响。蛋白与糖的质量比为1～8时,反应相同时间的乳清蛋白-麦芽糖中α-乳白蛋白和β-乳球蛋白的抗原性随蛋白与糖的质量比的下降而下降。     

喷射蒸煮水热处理提升大豆分离蛋白乳化性的研究

该文使用喷射蒸煮水热反应器进行大豆蛋白糖基化反应,在高温、高压的水热条件下,蛋白质与小分子单糖及双糖进行Mailard反应,生成共价复合物.结果显示生成的复合物比大豆蛋白乳化活性有所提升,其在高温、高盐的条件下乳化活性的变化较小.