Novel broad spectrum therapeutic glycans against Category B pathogens
针对 B 类病原体的新型广谱治疗聚糖
基本信息
- 批准号:7934513
- 负责人:
- 金额:$ 89.03万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2007
- 资助国家:美国
- 起止时间:2007-09-01 至 2014-11-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAdhesionsAnimalsBacteriaBindingBiomedical EngineeringCalicivirusCampylobacterCampylobacter jejuniCategoriesCell surfaceCellsChemicalsConsumptionDataDiarrheaDietEpidemicEpidemiologic StudiesEpitopesEscherichia coliExposure toFamilyForce of GravityGenerationsGlycoconjugatesHumanHuman MilkIn VitroIndividualInfectionInfection preventionInflammatory ResponseIntestinal MucosaLeadLinkMethodsMolecularMolecular WeightMucin-1 Staining MethodMucinsNational Institute of Allergy and Infectious DiseaseNorovirusOligosaccharidesOralPathogenesisPhasePlantsPolysaccharidesPopulationPopulations at RiskPre-Clinical ModelPreclinical TestingProductionResearchResistanceResistance developmentSeveritiesStagingStructureTaste PerceptionTechniquesTemperatureTestingTherapeuticTherapeutic AgentsTherapeutic UsesVibrioVibrio choleraeVirusYeastsanalogantimicrobial drugbiodefensecostdesigndrinkinghuman diseasein vivoinhibitor/antagonistinstrumentlarge scale productionmicroorganismnovelnovel therapeuticspathogenpathogen exposurepolylactosamineprebioticspreclinical studypreventprophylacticprototypequantumreceptorscale upsuccess
项目摘要
DESCRIPTION (provided by applicant):
The glycans (oligosaccharides and glycoconjugates) of human milk are powerful pathogen anti-adhesion compounds, and represent a novel class of antimicrobial agents. We propose to synthesize and test two of the most promising prototypes of fucosyl glycans (oligosaccharides and mucin) that naturally occur in human milk and have been shown, from in vitro, in vivo and molecular epidemiologic studies, to strongly inhibit NIAID Category B pathogens Campylobacter, Vibrio cholera, diarrheagenic Escherichia coli, and caliciviruses (noroviruses). These glycans function as receptor analogs that prevent infection by inhibiting pathogen binding to host cell surface glycans. Further, repeated pathogen exposure to such glycans does not result in resistance. Such glycans are stable for prolonged periods at room temperature, are intrinsically pleasant tasting, and could be produced and distributed economically as part of a drink or nutriment to individuals or populations at risk. A major roadblock to preclinical studies and human trials, however, has been the complexity and cost of synthesis of these fucosyl glycans. We propose to use recent breakthroughs in bioengineering for two generations of large-scale synthesis of fucosyl glycans in genetically modified microorganisms. Fucosyl oligosaccharides expressed in a bacterial construct will serve as standard synthetic monovalent inhibitors. A simultaneous but longer second generation of synthesis will be construction of a yeast that produces high molecular weight mucins whose polyvalent and multivalent expression of fucosylated moieties are expected to provide stronger and more broadly effective pathogen inhibition. The synthesis of these fucosyl glycans and their preclinical testing would be a quantum step towards a novel family of broadly effective therapeutics and prophylactics, would bring us to the threshold of human trials against Category B pathogens, and would represent a powerful new instrument for biodefense.
描述(由申请人提供):
人乳中的聚糖(寡糖和糖缀合物)是强效的病原体抗粘附化合物,代表了一类新型抗菌剂。我们建议合成和测试两个最有前途的原型岩藻糖基聚糖(寡糖和粘蛋白),天然存在于人乳中,并已被证明,从体外,体内和分子流行病学研究,强烈抑制NIAID类别B病原体弯曲杆菌,霍乱弧菌,大肠杆菌,和杯状病毒(诺如病毒)。这些聚糖作为受体类似物起作用,其通过抑制病原体与宿主细胞表面聚糖结合来预防感染。此外,病原体反复暴露于此类聚糖不会导致耐药性。这种聚糖在室温下长时间稳定,具有内在的宜人味道,并且可以作为饮料或营养物的一部分经济地生产和分配给处于风险中的个人或群体。然而,临床前研究和人体试验的一个主要障碍是合成这些岩藻糖基聚糖的复杂性和成本。我们建议利用生物工程的最新突破,在转基因微生物中大规模合成岩藻糖基聚糖。在细菌构建体中表达的岩藻糖基寡糖将用作标准的合成单价抑制剂。同时但更长的第二代合成将是构建产生高分子量粘蛋白的酵母,预期其岩藻糖基化部分的多价和多价表达提供更强和更广泛有效的病原体抑制。这些岩藻糖基聚糖的合成及其临床前测试将是迈向一个广泛有效的治疗剂和抗菌剂新家族的重要一步,将使我们进入针对B类病原体的人体试验的门槛,并将代表生物防御的强大新工具。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
DAVID S. NEWBURG其他文献
DAVID S. NEWBURG的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('DAVID S. NEWBURG', 18)}}的其他基金
CHARACTERIZATION OF SULFATIDES AND GAGS IN HUMAN MILK
母乳中硫化物和甘油的表征
- 批准号:
8365554 - 财政年份:2011
- 资助金额:
$ 89.03万 - 项目类别:
CHARACTERIZATION OF SULFATIDES AND OTHER LIPID CONJUGATES IN HUMAN MILK
人乳中硫苷脂和其他脂质结合物的表征
- 批准号:
8170925 - 财政年份:2010
- 资助金额:
$ 89.03万 - 项目类别:
Oligosaccharide moieties of human milk glycans that inhibit pathogens
抑制病原体的母乳聚糖的寡糖部分
- 批准号:
7740475 - 财政年份:2009
- 资助金额:
$ 89.03万 - 项目类别:
Oligosaccharide moieties of human milk glycans that inhibit pathogens
抑制病原体的母乳聚糖的寡糖部分
- 批准号:
8136058 - 财政年份:2009
- 资助金额:
$ 89.03万 - 项目类别:
CHARACTERIZATION OF SULFATIDES AND OTHER LIPID CONJUGATES IN HUMAN MILK: HIV
母乳中硫苷脂和其他脂质结合物的表征:HIV
- 批准号:
7955961 - 财政年份:2009
- 资助金额:
$ 89.03万 - 项目类别:
Oligosaccharide moieties of human milk glycans that inhibit pathogens
抑制病原体的母乳聚糖的寡糖部分
- 批准号:
7936219 - 财政年份:2009
- 资助金额:
$ 89.03万 - 项目类别:
Oligosaccharide moieties of human milk glycans that inhibit pathogens
抑制病原体的母乳聚糖的寡糖部分
- 批准号:
8494063 - 财政年份:2009
- 资助金额:
$ 89.03万 - 项目类别:
Oligosaccharide moieties of human milk glycans that inhibit pathogens
抑制病原体的母乳聚糖的寡糖部分
- 批准号:
8688286 - 财政年份:2009
- 资助金额:
$ 89.03万 - 项目类别:
CHARACTERIZATION OF SULFATIDES AND OTHER LIPID CONJUGATES IN HUMAN MILK: HIV
母乳中硫苷脂和其他脂质结合物的表征:HIV
- 批准号:
7723082 - 财政年份:2008
- 资助金额:
$ 89.03万 - 项目类别:
相似海外基金
How tensins transform focal adhesions into fibrillar adhesions and phase separate to form new adhesion signalling hubs.
张力蛋白如何将粘着斑转化为纤维状粘连并相分离以形成新的粘连信号中枢。
- 批准号:
BB/Y004841/1 - 财政年份:2024
- 资助金额:
$ 89.03万 - 项目类别:
Research Grant
Defining a role for non-canonical mTORC1 activity at focal adhesions
定义非典型 mTORC1 活性在粘着斑中的作用
- 批准号:
BB/Y001427/1 - 财政年份:2024
- 资助金额:
$ 89.03万 - 项目类别:
Research Grant
How tensins transform focal adhesions into fibrillar adhesions and phase separate to form new adhesion signalling hubs.
张力蛋白如何将粘着斑转化为纤维状粘连并相分离以形成新的粘连信号中枢。
- 批准号:
BB/Y005414/1 - 财政年份:2024
- 资助金额:
$ 89.03万 - 项目类别:
Research Grant
Development of a single-use, ready-to-use, sterile, dual chamber, dual syringe sprayable hydrogel to prevent postsurgical cardiac adhesions.
开发一次性、即用型、无菌、双室、双注射器可喷雾水凝胶,以防止术后心脏粘连。
- 批准号:
10669829 - 财政年份:2023
- 资助金额:
$ 89.03万 - 项目类别:
Regulating axon guidance through local translation at adhesions
通过粘连处的局部翻译调节轴突引导
- 批准号:
10587090 - 财政年份:2023
- 资助金额:
$ 89.03万 - 项目类别:
Improving Maternal Outcomes of Cesarean Delivery with the Prevention of Postoperative Adhesions
通过预防术后粘连改善剖宫产的产妇结局
- 批准号:
10821599 - 财政年份:2023
- 资助金额:
$ 89.03万 - 项目类别:
Regulating axon guidance through local translation at adhesions
通过粘连处的局部翻译调节轴突引导
- 批准号:
10841832 - 财政年份:2023
- 资助金额:
$ 89.03万 - 项目类别:
Prevention of Intraabdominal Adhesions via Release of Novel Anti-Inflammatory from Surface Eroding Polymer Solid Barrier
通过从表面侵蚀聚合物固体屏障中释放新型抗炎剂来预防腹内粘连
- 批准号:
10532480 - 财政年份:2022
- 资助金额:
$ 89.03万 - 项目类别:
I-Corps: A Sprayable Tissue-Binding Hydrogel to Prevent Postsurgical Cardiac Adhesions
I-Corps:一种可喷雾的组织结合水凝胶,可防止术后心脏粘连
- 批准号:
10741261 - 财政年份:2022
- 资助金额:
$ 89.03万 - 项目类别:
Sprayable Polymer Blends for Prevention of Site Specific Surgical Adhesions
用于预防特定部位手术粘连的可喷涂聚合物共混物
- 批准号:
10674894 - 财政年份:2022
- 资助金额:
$ 89.03万 - 项目类别: