Integrated, Modular Equipment for Large-scale and Small-scale Peptide Synthesis

用于大规模和小规模肽合成的集成模块化设备

• 批准号: 7389098
• 负责人: ALAN J WARING
• 金额: $ 22.44万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2009-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7389098
• 关键词: Alzheimer' s Disease; Amyloid beta-Protein; Antioxidants; Atherosclerosis; Autoimmune Diseases; Biomedical Research; Chemicals; Development; Drug Delivery Systems; Equipment; Freeze Drying; HIV-1; Herpesviridae; High Pressure Liquid Chromatography; Human; Image; Infection prevention; Influenza; Institution; Iron; Laboratories; Lupus; Mediating; Pathogenesis; Patients; Peptide Synthesis; Peptides; Production; Property; Quantum Dots; Risk; Safety; System; anthrax toxin; cell injury; disulfide bond; hepcidin; improved; instrumentation; medical schools; nanocomposite; novel; receptor; retrocyclin; uptake

DESCRIPTION (provided by applicant): The instrumentation requested will equip a Peptide Core Laboratory at the David Geffen School of Medicine at UCLA, one of the nation's premier biomedical research institutions. It will consist of a multiple peptide synthesizer for small and intermediate scale peptide production, a preparative HPLC unit with integrated on- line mass spec system, freeze drying apparatus, and a chemical safety hood. Peptides produced in this facility would be used to study: a) hepcidin, a recently discovered 23-residue peptide that is a master regulator of iron uptake and utilization in humans; b) retrocyclins, cyclic octadecapeptides that prevent infection by HIV-1, influenza and herpes viruses; c) beta-amyloid, a peptide whose properties are involved in the pathogenesis of Alzheimer's Disease; d) antioxidant peptides, such as D4F, with the potential to decrease the risk of atherosclerosis; e) immunoregulatory peptides, that could eventually improve the treatment of patients with autoimmune disorders, such as lupus; f) peptides that can block the receptor-mediated ability of anthrax toxins to enter and damage cells; and g) peptides that can functionalize novel nanocomposite materials ("quantum dots"), and promote their development as novel imaging and drug-delivery agents. Each of these projects depends on peptides that are not available "off-the-shelf". Consequently, the studies are often impeded by the expense or difficulty of obtaining peptides that may be cyclic (retrocyclins, D4F), or have multiple disulfide bonds (retrocyclins and hepcidin).

描述（由申请人提供）：所需的仪器将装备加州大学洛杉矶分校大卫格芬医学院的肽核心实验室，该学院是美国首屈一指的生物医学研究机构之一。它将由用于中小规模肽生产的多肽合成仪、带有集成在线质谱系统的制备型 HPLC 装置、冷冻干燥装置和化学安全罩组成。该设施生产的肽将用于研究：a) 铁调素，一种最近发现的 23 个残基肽，是人类铁吸收和利用的主要调节剂； b) 逆环素、环十八肽，可预防 HIV-1、流感和疱疹病毒感染； c) β-淀粉样蛋白，一种肽，其特性与阿尔茨海默病的发病机制有关； d) 抗氧化肽，例如 D4F，具有降低动脉粥样硬化风险的潜力； e) 免疫调节肽，最终可以改善狼疮等自身免疫性疾病患者的治疗； f) 可以阻断炭疽毒素受体介导的能力进入并损伤细胞的肽； g) 可以使新型纳米复合材料（“量子点”）功能化的肽，并促进其作为新型成像和药物递送剂的发展。 这些项目中的每一个都依赖于无法“现成”获得的肽。因此，这些研究常常因获取可能是环状的肽（逆环素、D4F）或具有多个二硫键（逆环素和铁调素）的费用或困难而受到阻碍。

项目成果

Deep Coverage of Global Protein Expression and Phosphorylation in Breast Tumor Cell Lines Using TMT 10-plex Isobaric Labeling.

• DOI: 10.1021/acs.jproteome.6b00374
• 发表时间: 2017-03-03
• 期刊: Journal of proteome research
• 影响因子: 4.4
• 作者: Huang FK;Zhang G;Lawlor K;Nazarian A;Philip J;Tempst P;Dephoure N;Neubert TA
• 通讯作者: Neubert TA