Novel Ribostamycins and SAR Study of Ring III Aminosugar
新型核霉素和环III氨基糖的SAR研究
基本信息
- 批准号:7340550
- 负责人:
- 金额:$ 12.93万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2004
- 资助国家:美国
- 起止时间:2004-03-01 至 2010-02-28
- 项目状态:已结题
- 来源:
- 关键词:AcidsAffinityAmerican Type Culture CollectionAmikacinAmino AcidsAmino SugarsAminoglycoside AntibioticsAminoglycoside resistanceAminoglycosidesAnthrax diseaseAnti-Bacterial AgentsAntibioticsAntifungal AgentsAntineoplastic AgentsAntiviral AgentsAreaBacillus (bacterium)Bacillus subtilisBacteriaBindingBinding SitesBiologicalBiological AssayCarbohydratesCellsChargeCollaborationsCoupledDeoxy SugarsDevelopmentDrug DesignDrug resistanceDrug-sensitiveEnterococcus faecalisEnzymesEscherichia coliEvaluationFluorescenceFutureGentamicinsGoalsHIVHybridsIn VitroKnowledgeLaboratoriesLeadLearningLibrariesMethodsModificationMultiple drug resistant Mycobacteria TuberculosisMycobacterium smegmatisMycobacterium tuberculosisNational SecurityNeomycinObject AttachmentOligopeptidesPhasePreparationProtocols documentationPublic HealthPyranmycinRNARangeResearchResearch PersonnelResistanceRibosomal RNARibostamycinRoentgen RaysSamplingScreening procedureServicesSolidStaphylococcus aureusStreptomycinStructureStructure-Activity RelationshipTestingWorkantibiotic designantimicrobialbacterial resistancebasecarbohydrate receptorcostcytotoxicitydesignexperienceimprovedin vivointerestnovelpathogenpractical applicationpyranosesugar
项目摘要
DESCRIPTION (provided by applicant): Carbohydrate research can contribute profound impacts in various fields although the synthesis of carbohydrate derivatives has been the major obstacle that impedes the progress in this area. Through our experience and effort, we have achieved our preliminary projected goals: synthesis of aminosugars/deoxysugars library, preparation of aminosugars/deoxysugars containing molecules with practical applications, and the studies of biological implications with these aminosugars/deoxysugars containing molecules. We are one of the few groups capable of creating such diverse unusual sugar and aminoglycoside libraries. After successfully achieving our initial goal of generating aminosugar/deoxysugar library, we have moved into one of the envisioned applications of unusual sugars: synthesizing a library of pyranmycin, novel aminoglycoside antibiotics. Compared to previous work, our pyranmycin designs provide the only examples with antibacterial activity close to neomycin (low micromole), and with much-improved acid stability. The later may potentially lead to the reduction of the cytotoxicity known to be associated with aminoglycoside antibiotics. Using synthetic approaches, we intend to synthesize two more structural entities coupled with a solid phase parallel synthesis of oligopeptides for the development of the general aminoglycoside designs against various strains of resistant bacteria, and with lower cytotoxicity. These are very challenging but interesting and important tasks. We have proposed several practical synthetic methods for our objectives. We have established our own facilities or collaborations for evaluating the antibacterial activity of our pyranmycin constructs in vivo and in whole cell based. We have learned solid knowledge in carbohydrate synthesis and aminoglycoside antibiotic design through our research. We wish to learn more regarding the influence of modulating the interactions, charge-charge and van der Waals, and apply the finding for future drug designs. It is our conviction that our proposed research will provide breakthroughs in carbohydrate-related fields, and pave the way to a broader research ranging from basic scientific studies like carbohydrates and receptors interaction to practical applications regarding the issues of public health and national security, such as, the development of clinically important unusual sugar-containing antibacterial (against anthrax, MDR-TB), antiviral (against HIV), antifungal, and anticancer agents.
描述(由申请人提供):碳水化合物的研究可以在各个领域产生深远的影响,尽管碳水化合物衍生物的合成一直是阻碍该领域进展的主要障碍。通过我们的经验和努力,我们已经实现了我们的初步预期目标:合成氨基糖/脱氧糖库,制备具有实际应用的含氨基糖/脱氧糖分子,以及研究这些含氨基糖/脱氧糖分子的生物学意义。我们是为数不多的能够创建如此多样的不寻常的糖和氨基糖苷图书馆的小组之一。在成功实现了生成氨基糖/脱氧糖文库的最初目标后,我们已经进入了不寻常糖的设想应用之一:合成吡喃霉素(新型氨基糖苷类抗生素)文库。与以前的工作相比,我们的吡喃霉素设计提供了唯一的抗菌活性接近新霉素(低微摩尔)的例子,并大大提高了酸稳定性。后者可能潜在地导致已知与氨基糖苷类抗生素相关的细胞毒性降低。使用合成方法,我们打算合成两个以上的结构实体,再加上固相平行合成的寡肽的一般氨基糖苷类药物的设计开发对各种菌株的耐药细菌,并具有较低的细胞毒性。这些都是非常具有挑战性,但有趣和重要的任务。我们提出了几种实用的合成方法,我们的目标。我们已经建立了自己的设施或合作,以评估我们的吡喃霉素构建体在体内和基于全细胞的抗菌活性。通过我们的研究,我们在碳水化合物合成和氨基糖苷类抗生素设计方面积累了扎实的知识。我们希望了解更多关于调节相互作用、电荷-电荷和货车范德华力的影响,并将发现应用于未来的药物设计。我们相信,我们提出的研究将在碳水化合物相关领域提供突破,并为更广泛的研究铺平道路,从基础科学研究(如碳水化合物和受体相互作用)到有关公共卫生和国家安全问题的实际应用(如临床上重要的不寻常的含糖抗菌药物的开发)。(针对炭疽、MDR-TB)、抗病毒剂(针对HIV)、抗真菌剂和抗癌剂。
项目成果
期刊论文数量(11)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Synthesis and antibacterial activity of pyranmycin derivatives with N-1 and O-6 modifications.
N-1和O-6修饰吡喃霉素衍生物的合成及其抗菌活性。
- DOI:10.1016/j.bmc.2007.08.059
- 发表时间:2007
- 期刊:
- 影响因子:3.5
- 作者:Li,Jie;Chiang,Fang-I;Chen,Hsiao-Nung;Chang,Cheng-WeiTom
- 通讯作者:Chang,Cheng-WeiTom
Synthesis of novel aminoglycosides via allylic azide rearrangement for investigating the significance of 2'-amino group.
通过烯丙基叠氮化物重排合成新型氨基糖苷以研究 2-氨基的重要性。
- DOI:10.1016/j.bmc.2010.01.027
- 发表时间:2010
- 期刊:
- 影响因子:3.5
- 作者:Zhang,Jianjun;Litke,Anthony;Keller,Katherine;Rai,Ravi;Chang,Cheng-WeiTom
- 通讯作者:Chang,Cheng-WeiTom
Surprising alteration of antibacterial activity of 5"-modified neomycin against resistant bacteria.
- DOI:10.1021/jm800997s
- 发表时间:2008-12-11
- 期刊:
- 影响因子:7.3
- 作者:Zhang J;Chiang FI;Wu L;Czyryca PG;Li D;Chang CW
- 通讯作者:Chang CW
Synthesis and combinational antibacterial study of 5''-modified neomycin.
5-修饰新霉素的合成及联合抗菌研究。
- DOI:10.1038/ja.2009.66
- 发表时间:2009
- 期刊:
- 影响因子:0
- 作者:Zhang,Jianjun;Keller,Katherine;Takemoto,JonY;Bensaci,Mekki;Litke,Anthony;Czyryca,PrzemyslawGreg;Chang,Cheng-WeiTom
- 通讯作者:Chang,Cheng-WeiTom
Antifungal Amphiphilic Aminoglycosides.
- DOI:10.1039/c4md00078a
- 发表时间:2014-08-01
- 期刊:
- 影响因子:0
- 作者:Chang CW;Takemoto JY
- 通讯作者:Takemoto JY
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CHENG-WEI T CHANG其他文献
CHENG-WEI T CHANG的其他文献
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{{ truncateString('CHENG-WEI T CHANG', 18)}}的其他基金
Novel Ribostamycins and SAR Study of Ring III Aminosugar
新型核霉素及环III氨基糖的SAR研究
- 批准号:
7023762 - 财政年份:2004
- 资助金额:
$ 12.93万 - 项目类别:
Novel Ribostamycins and SAR Study of Ring III Aminosugar
新型核霉素及环III氨基糖的SAR研究
- 批准号:
6861100 - 财政年份:2004
- 资助金额:
$ 12.93万 - 项目类别:
Novel Ribostamycins and SAR Study of Ring III Aminosugar
新型核霉素和环III氨基糖的SAR研究
- 批准号:
7195772 - 财政年份:2004
- 资助金额:
$ 12.93万 - 项目类别:
Novel Ribostamycins and SAR Study of Ring III Aminosugar
新型核霉素及环III氨基糖的SAR研究
- 批准号:
6770744 - 财政年份:2004
- 资助金额:
$ 12.93万 - 项目类别:
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