Mass spectrometric investigation of biomolecules and dru

生物分子和药物的质谱研究

• 批准号: 7337596
• 负责人: Sonja Hess
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7337596
• 关键词: Mass; spectrometric; investigation; biomolecules; dru

In our Facility, we use mass spectrometry to analyze and characterize biomolecules such as proteins and DNA. We also maintain a small molecule unit that analyzes chemical drug candidates synthesized by various researchers. We provide scientific and technical support in these areas. Furthermore, we successfully promote collaborations to increase our understanding of fundamental biological processes, mostly related but not limited to diabetes, digestive and kidney diseases. We provided analyses to more than 50 principal investigators of our Institute. Many of these analyses are considered to be service and do not result in any publication. Nevertheless, some of the identifications that we perform are considered significant scientific contributions. Next to the support that we provide for other investigators, we have also successfully developed an independent research program. The techniques that we have developed for the determination of the secretory proteome of adipocytes have recently been applied to the determination of the secretory proteome of podocytes and the determinatin of the lipid droplet proteome in rat liver cells. We have concluded a study describing the genetic requirements for growth of E. coli on methyl-alph-D-glucopyranoside and the five alpha-D-glucosyl-D-fructose isomers of sucrose. We also have concluded a study on the cerebrospinal fluid proteome associated with chronic fatigue and related syndromes, which yielded the first predictive biomarkers for these syndromes. Using a logisitic model, we found that detection of >1 of a select set of 5 CFS-related proteins predicted CFS status with 80% concordance. Last but not least, we have expanded on our previously established protein-ligand interaction studies using HIV-1 Gag with assembly factors. Using a similar footprinting method, we also studied the hyperphosphorylation-induced conformational changes of full length native and hyperphosphorylated hRPA (human replication protein A). We found that three residues in the DNA binding domain B (K343, R335 and R382) were significantly shielded by hyperphosphorylation when compared to native hRPA. This led us to conclude that significant conformational changes involving the ssDNA binding cleft are induced after hyperphosphorylation.

在我们的设施中，我们使用质谱仪来分析和表征生物分子，如蛋白质和DNA。我们还保留了一个小分子单元，用于分析由不同研究人员合成的化学候选药物。我们在这些领域提供科学和技术支持。此外，我们成功地促进了合作，以增加我们对基本生物过程的了解，这些过程主要与但不限于糖尿病、消化系统和肾脏疾病有关。 我们向我们研究所的50多名主要研究人员提供了分析。这些分析中的许多被认为是服务的，不会导致任何出版物。 然而，我们进行的一些鉴定被认为是重大的科学贡献。除了我们为其他研究人员提供的支持外，我们还成功地开发了一个独立的研究计划。 我们建立的脂肪细胞分泌蛋白质组的测定技术最近已应用于足细胞分泌蛋白质组的测定和大鼠肝细胞脂滴蛋白质组的测定。 我们已经完成了一项研究，描述了大肠杆菌对甲基-α-D-吡喃葡萄糖苷和蔗糖的五个α-D-葡萄糖基-D-果糖异构体的遗传要求。 我们还完成了一项与慢性疲劳和相关综合征相关的脑脊液蛋白质组的研究，这项研究产生了第一个预测这些综合征的生物标志物。使用逻辑模型，我们发现检测一组精选的5个CFS相关蛋白中的&gt；1预测CFS状态具有80%的一致性。 最后但并非最不重要的是，我们扩大了我们以前建立的蛋白质-配体相互作用的研究，使用带有组装因子的HIV-1 Gag。 利用类似的足迹法，我们还研究了过度磷酸化诱导的全长天然和过度磷酸化的HrpA(人类复制蛋白A)的构象变化。我们发现，与天然HrpA相比，DNA结合结构域B的三个残基(K343、R335和R382)被过度磷酸化显著屏蔽。这使我们得出结论，涉及单链DNA结合裂解的显著构象变化是在过度磷酸化后引起的。

项目成果

Thermolytic CpG-containing DNA oligonucleotides as potential immunotherapeutic prodrugs.

含热溶解CpG的DNA寡核苷酸作为潜在的免疫治疗前药。

• DOI: 10.1093/nar/gki657
• 发表时间: 2005
• 期刊: NUCLEIC ACIDS RESEARCH
• 影响因子: 14.9
• 作者: Grajkowski, A;Pedras-Vasconcelos, J;Wang, VV;Ausín, C;Hess, S;Verthelyi, D;Beaucage, SL
• 通讯作者: Beaucage, SL

2,2,5,5-tetramethylpyrrolidin-3-one-1-sulfinyl group for 5'-hydroxyl protection of deoxyribonucleoside phosphoramidites in the solid-phase preparation of DNA oligonucleotides.

2,2,5,5-四甲基吡咯烷-3-酮-1-亚磺酰基在 DNA 寡核苷酸固相制备中对脱氧核糖核苷亚磷酰胺进行 5-羟基保护。

• DOI: 10.1021/ja048377i
• 发表时间: 2004
• 期刊: Journal of the American Chemical Society
• 影响因子: 15
• 作者: Marchan,Vicente;Cieyylak,Jacek;Livengood,Victor;Beaucage,SergeL
• 通讯作者: Beaucage,SergeL

Peptide fragmentation by corona discharge induced electrochemical ionization.

• DOI: 10.1016/j.jasms.2010.08.018
• 发表时间: 2010-12
• 期刊: Journal of the American Society for Mass Spectrometry
• 影响因子: 3.2
• 作者: Lloyd JR;Hess S
• 通讯作者: Hess S

Novel valproic acid derivatives with potent differentiation-inducing activity in myeloid leukemia cells.

• DOI: 10.1016/j.leukres.2006.01.009
• 发表时间: 2006-09
• 期刊: Leukemia research
• 影响因子: 2.7
• 作者: H. Deubzer;B. Busche;Gabi Rönndahl;D. Eikel;M. Michaelis;J. Cinatl;S. Schulze;H. Nau;O. Witt

A combined top-down and bottom-up MS approach for the characterization of hemoglobin variants in Rhesus monkeys.

用于表征恒河猴血红蛋白变异的自上而下和自下而上相结合的 MS 方法。

• DOI: 10.1002/pmic.201000161
• 发表时间: 2010
• 期刊: Proteomics
• 影响因子: 3.4
• 作者: Hüttenhain,Ruth;Hess,Sonja
• 通讯作者: Hess,Sonja