Mass spectrometric investigation of biomolecules and dru

生物分子和药物的质谱研究

基本信息

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
项目类别：
财政年份：
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

项目摘要

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，我们使用质谱法分析和表征生物分子，例如蛋白质和DNA。我们还维护一个小分子单位，该单元分析了各种研究人员合成的化学药物候选物。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，以增加对基本生物学过程的理解，主要是相关但不限于糖尿病，消化和肾脏疾病。我们向研究所的50多位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，并且不会导致任何出版物。然而，我们执行的一些标识被认为是重要的科学贡献。在我们为其他研究人员提供的支持之后，我们还成功地制定了一个独立的研究计划。我们为测定脂肪细胞分泌蛋白组开发的技术最近已应用于确定足细胞的分泌蛋白质组和大鼠肝细胞中脂质滴蛋白蛋白蛋白蛋白蛋白的确定蛋白。我们总结了一项研究，描述了大肠杆菌在甲基-Alph-D-葡萄糖苷上的遗传需求和蔗糖的五个α-D-葡萄糖基-D-果糖异构体。我们还综述了一项关于与慢性疲劳和相关综合征相关的脑脊液蛋白质组蛋白质组的研究，该研究产生了这些综合征的第一个预测生物标志物。使用Logisitic模型，我们发现选择了5个CFS相关蛋白的选择集的> 1的检测预测CFS状态具有80％的一致性。最后但并非最不重要的一点是，我们使用带有组装因子的HIV-1 GAG进行了以前确定的蛋白质 - 配体相互作用研究。使用类似的足迹方法，我们还研究了全长天然和高磷酸化HRPA（人类复制蛋白A）的高磷酸化构象变化。我们发现，与天然HRPA相比，DNA结合结构域B（K343，R335和R382）中的三个残基显着屏蔽。这使我们得出结论，涉及ssDNA结合裂口的显着构象变化是在过度磷酸化后诱导的。

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Thermolytic CpG-containing DNA oligonucleotides as potential immunotherapeutic prodrugs.

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
通讯作者：
H. Deubzer;B. Busche;Gabi Rönndahl;D. Eikel;M. Michaelis;J. Cinatl;S. Schulze;H. Nau;O. Witt

A Universal HPLC-MS Method to Determine the Stereochemistry of Common and Unusual Amino Acids.

确定常见和不常见氨基酸立体化学的通用 HPLC-MS 方法。