Chemical Biology Core

化学生物学核心

基本信息

批准号：
10115663
负责人：
Harshani R Lawrence
金额：
$ 9.64万
依托单位：
H. LEE MOFFITT CANCER CTR & RES INST
依托单位国家：
美国
项目类别：
财政年份：
1998
资助国家：
美国
起止时间：
1998-02-18 至 2022-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10115663
关键词：
ACK1 Gene Affinity Analytical Chemistry Animals Antineoplastic Agents Award Biochemical Biochemistry Biology Calorimetry Cancer Biology Cancer Center Cancer Center Support Grant Chemicals Chemistry Clinic Cloning Collaborations Communication Complex Consultations Crystallization Crystallography Data Data Analyses Development Drug Design Drug Interactions Drug Kinetics Ensure Equipment Experimental Designs Formulation Funding Generations Goals Infrastructure Knowledge Lead Libraries Ligands Malignant Neoplasms Molecular Peer Review Peptides Pharmaceutical Chemistry Phosphotyrosine Production Property Protein Chemistry Proteins Proteomics Publications Research Research Design Research Project Grants Research Proposals Resolution Resources Roentgen Rays Scanning Services Signal Pathway Specificity Structural Protein Structure Structure-Activity Relationship Surface Plasmon Resonance Synthesis Chemistry TP53 gene Technology Time Titrations Training Tyrosine Kinase Inhibitor Work X-Ray Crystallography anti-cancer base biophysical properties cancer cell casein kinase chemical synthesis design drug development drug discovery efficacy study experience improved inhibitor/antagonist instrument instrumentation kinase inhibitor lead candidate lead optimization member novel pre-clinical programs protein function protein purification protein structure safety study scale up screening small molecule small molecule libraries tumorigenesis

项目摘要

PROJECT SUMMARY The Chemical Biology Core (CBC) offers Moffitt Cancer Center (MCC) members access to state-of-the-art technology, instruments, expertise and infrastructure necessary for studying proteins involved in tumorigenesis. The CBC also provides synthetic and medicinal chemistry services for synthesizing chemical probes and to develop lead candidates into compounds that are suitable for pre-clinical cancer efficacy and safety studies. The specific aims of the CBC are to: 1) assist in study design, implementation of synthesis of chemical probes, X-ray crystallography, and protein production via consultation and collaborations; 2) provide members with resources to study the structure of proteins involved in tumorigenesis; and 3) provide access and training on state-of-the-art instrumentation to members. The CBC is composed of two highly specialized sections, Chemistry and Protein Crystallography, which provide services in Synthetic/Medicinal Chemistry, Protein Crystallography, and Biochemistry. The CBC employs five experienced full-time staff, who provide expertise in chemistry, drug discovery and development, protein production, crystallography and biochemistry, and cancer biology. Chemistry services offered by the CBC include: 1) synthesis of focused libraries for hit-to-lead-optimization of new anti-cancer compounds; 2) synthesis of complex small molecules as chemical probes; 3) medicinal chemistry and scale-up synthesis, to provide pre-clinical compounds for potency, selectivity, efficacy and safety studies; 4) analytical chemistry services, to determine physicochemical properties of potent compounds; 5) and synthesis of tagged chemical probes for affinity-based chemical proteomics studies. The CBC also provides support for cloning, expression, large-scale purification of target proteins, X-ray crystallography, high-resolution structure determination, structure-guided synthesis, protein-protein and protein-ligand/drug interactions, and structure of protein-inhibitor complexes. Facilitating this work, the CBC provides members access to high-end instrumentation and associated training. Over the past five years, chemistry, protein production, and crystallography services have supported the projects of 49 members, including services critical for 14 new research grant awards to members. The CBC contributed to 52 publications via synthesis of compounds, protein production, and high-end instrumentation, and core staff were co-authors on the publications of 24 members. During the most recent fiscal year, the CBC provided service for 23 members in four research programs: CBMM (12 members), CBE (6), IMM (3), and CE (2). Regarding use of the CBC, 81% was by peer-review-funded members. The CBC also provided preliminary data, technical sections, and consultation for 21 research proposals during the most recent year. The CBC is supported by institutional and CCSG funds and will continue to provide outstanding chemical biology and state-of-the-art technologies to MCC members.

项目摘要化学生物学核心（CBC）为莫菲特癌症中心（MCC）成员提供了最先进的访问权限研究涉及的蛋白质所需的技术，工具，专业知识和基础设施肿瘤发生。 CBC还提供合成和药物化学服务以合成化学探针并将铅候选者发展成适合临床前癌症的化合物功效和安全研究。 CBC的具体目的是：1）协助研究设计，实施通过咨询和协作的合成化学探针，X射线晶体学和蛋白质产生的合成； 2）为成员提供研究参与肿瘤发生的蛋白质结构的资源； 3）提供对成员的最先进仪器的访问和培训。 CBC由两个高度专业的切片，化学和蛋白质晶体学组成，它们是提供合成/药物化学，蛋白质晶体学和生物化学的服务。 CBC 雇用五名经验丰富的全职员工，他们提供化学，药物发现和开发，蛋白质产生，晶体学和生物化学和癌症生物学。化学 CBC提供的服务包括：1）综合专注的库，以命中率高于新的抗癌化合物； 2）合成复杂的小分子作为化学探针； 3）药用化学和扩大合成，以提供临床前化合物，以提高效力，选择性，功效和安全研究； 4）分析化学服务，确定有效的物理化学特性化合物； 5）并合成基于亲和力的化学蛋白质组学研究的标记化学探针。 CBC还提供了克隆，表达，靶蛋白的大规模纯化，X射线晶体学，高分辨率结构确定，结构引导的合成，蛋白质 - 蛋白质和蛋白质 - 配体/药物相互作用以及蛋白质抑制剂复合物的结构。促进这项工作， CBC为会员提供了高端仪器和相关培训的访问。在过去的五个年份，化学，蛋白质生产和晶体学服务支持了49个项目成员，包括对成员14个新研究授予奖励至关重要的服务。加拿大广播公司为 52通过合成化合物，蛋白质生产和高端仪器以及核心人员的出版物是24名成员出版物的合着者。在最近的财政年度，CBC提供了在四个研究计划中为23名成员提供服务：CBMM（12名成员），CBE（6），IMM（3）和CE（2）。关于使用CBC，有81％的人是由同行评估资助的成员。 CBC还提供了初步最近一年，有关21项研究建议的数据，技术部分和咨询。 CBC 得到机构和CCSG资金的支持，将继续提供出色的化学生物学和对MCC成员的最先进技术。