PepSAVI-MS for discovery of novel botanical antimicrobial peptides

PepSAVI-MS 用于发现新型植物抗菌肽

• 批准号: 10572713
• 负责人: Leslie M. Hicks
• 金额: $ 6.8万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-05-01 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10572713
• 关键词: Address; Anti-Bacterial Agents; Anti-Infective Agents; Antibiotic Therapy; Antibiotics; Antimicrobial Resistance; Bacteria; Bacterial Infections; Biological; Biological Assay; Biological Products; Biological Testing; Botanicals; Breathing; Characteristics; Chemicals; Chemistry; Clinical; Colistin; Community Hospitals; Coupled; Detection; Developing Countries; Drug Kinetics; Drug resistance; ESKAPE pathogens; Effectiveness; Enterobacteriaceae Infections; Environment; Evolution; Future; Goals; Heel; Hybrids; Informatics; Laboratories; Lead; Length; Libraries; Life; Mass Spectrum Analysis; Medicine; Metabolic; Methods; Microbe; Mining; Modernization; Modification; Molecular; Multi-Drug Resistance; Natural Products; Nature; Nosocomial Infections; Organism; Penetration; Peptides; Pharmaceutical Preparations; Pharmacology; Phenotype; Plant Extracts; Plants; Population; Post-Translational Protein Processing; Primary Health Care; Property; Proteins; Proteomics; Resources; Ribosomes; Savings; Signal Transduction; Soil; Source; Specificity; Statistical Models; Streptomycin; Techniques; Testing; Therapeutic; Tissues; Validation; Work; antimicrobial; antimicrobial drug; antimicrobial peptide; base; carbapenem-resistant Enterobacteriaceae; data handling; drug discovery; experimental study; falls; genome sequencing; immunogenicity; improved; infectious disease treatment; innovative technologies; instrumentation; knowledge base; lens; microbial; microorganism; novel; novel therapeutics; peptidomimetics; relative cost; scaffold; screening; small molecule therapeutics; therapy development

ABSTRACT The continued evolution of antimicrobial resistance emphasizes the dire need for discovery of antibiotic therapeutics with novel mechanisms of action. Technological advances in genome sequencing, drug library creation, and structural informatics have not advanced infectious disease treatments sufficiently. While natural products have long served as inspiration for novel therapeutic scaffolds, we posit peptide-derived entities offer great potential to address current needs due to their unique mechanisms of action, penetration and selectively. Herein, we describe our PepSAVI-MS pipeline to discover and characterize peptides with antimicrobial activity through implementation of a hybrid bioassay-guided/peptidomics platform. We directly identify botanical peptides contributing to bioactivity profiles using robust microbial bioassays optimized for peptide screening and using a mass spectrometry-based peptidomics approach coupled to statistical modeling and informatics to identify and further characterize these peptides at the molecular level. These potential lead compounds are then tested against an extensive panel of clinical ESKAPE pathogens, as well as for favorable drug characteristics and determination of mechanism-of-action. Our platform enables robust mining of plants and other natural sources for peptidyl species with unique or broad-spectrum anti-infective properties and has the potential to lead to the discovery of novel chemistries at the forefront of modern drug discovery.

抽象的 抗菌耐药性的持续演变强调了发现抗生素的迫切需求 具有新型作用机理的治疗学。基因组测序的技术进步，药物文库 创造和结构信息学还没有足够的传染病治疗。虽然很自然 长期以来，产品一直是新型治疗脚手架的灵感，我们提出了肽衍生的实体 由于其独特的作用机制，穿透性和有选择性的方式，可以解决当前需求的巨大潜力。 在此，我们描述了我们的百事可乐MS管道，以发现和表征具有抗菌活性的肽 通过实施混合生物测定指导/肽组学平台。我们直接识别植物 使用可用于肽筛查优化的鲁棒微生物生物测定的肽促成生物活性谱 并使用基于质谱的肽学方法方法结合了统计建模和信息学 在分子水平上识别并进一步表征这些肽。这些潜在的铅化合物是 然后针对广泛的临床Eskape病原体进行测试，以及有利的药物 行动机理的特征和确定。我们的平台可实现强大的植物开采和 具有独特或广谱抗感染特性的肽基物种的其他天然来源，具有 可能导致在现代药物发现的最前沿发现新颖的化学物质。

项目成果

The Greater Celandine: Identification and Characterization of an Antimicrobial Peptide from Chelidonium majus.

• DOI: 10.1021/acs.jnatprod.3c00939
• 发表时间: 2024-02
• 期刊: Journal of natural products
• 影响因子: 5.1
• 作者: Patric W. Sadecki;Garrett D Laws;Johnathon J Morgan;A. Wommack;R. Nawrot;Leslie M Hicks

Exploring the Diversity of Cysteine-Rich Natural Product Peptides via MS/MS Fingerprint Ions.

• DOI: 10.1021/jasms.0c00078
• 发表时间: 2020-09-02
• 期刊: Journal of the American Society for Mass Spectrometry
• 影响因子: 3.2
• 作者: Parsley NC;Williams OL;Hicks LM
• 通讯作者: Hicks LM

Metabolomic characterization of Pseudomonas protegenssecretions for identification of biopesticides against Bacterial Panicle Blight of rice.

保护假单胞菌分泌物的代谢组学特征，用于鉴定抗水稻细菌性穗枯病的生物农药。

• 发表时间: 2022
• 期刊: FASEB journal : official publication of the Federation of American Societies for Experimental Biology
• 作者: Balboa,SamanthaJ;Vierengel,Maia;Gates,Kristen;Rojas,Clemencia;Hicks,Leslie
• 通讯作者: Hicks,Leslie

The "PepSAVI-MS" Pipeline for Natural Product Bioactive Peptide Discovery.

• DOI: 10.1021/acs.analchem.6b03625
• 发表时间: 2017-01-17
• 期刊: Analytical chemistry
• 影响因子: 7.4
• 作者: Kirkpatrick CL;Broberg CA;McCool EN;Lee WJ;Chao A;McConnell EW;Pritchard DA;Hebert M;Fleeman R;Adams J;Jamil A;Madera L;Strömstedt AA;Göransson U;Liu Y;Hoskin DW;Shaw LN;Hicks LM
• 通讯作者: Hicks LM

Mass Spectrometric Identification of Antimicrobial Peptides from Medicinal Seeds.

• DOI: 10.3390/molecules26237304
• 发表时间: 2021-12-01
• 期刊: Molecules (Basel, Switzerland)
• 作者: Moyer TB;Brechbill AM;Hicks LM
• 通讯作者: Hicks LM