Development of Antimicrobial Peptides as Topical Microbicides

抗菌肽作为局部杀菌剂的开发

基本信息

批准号：
7893461
负责人：
Robert Walter Buckheit
金额：
$ 20.04万
依托单位：
IMQUEST BIOSCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-07-01 至 2012-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7893461
关键词：
Accounting Acquired Immunodeficiency Syndrome Address Algorithms Amino Acid Motifs Amino Acids Amphibia Animal Model Anti-Infective Agents Antiviral Agents BMAP-27 Bacteria Biochemical Bioinformatics Biological Biological Assay Biology CAP18 lipopolysaccharide-binding protein Cataloging Catalogs Cattle Cells Cervical Cessation of life Clinical Clinical Trials Collection Communities Cream Data Databases Defensins Derivation procedure Developing Countries Development Dose Drug Formulations Drug Kinetics Engineering Ensure Epithelial Cells Evaluation Face Female Funding Funding Agency Gel Goals HIV HIV Infections HIV-1 Human Human Herpesvirus 2 Immune response Immunologics Individual Infection Infectious Agent Insecta Knowledge Laboratories Lactobacillus Lead Life Local Microbicides Mammals Medical center Methods Microbiology Mining Modeling Modification Molecular Nebraska Organism Oryctolagus cuniculus Outcome Outcome Study Parasites Parents Peer Review Peptides Performance Pharmacology and Toxicology Phase Positioning Attribute Principal Investigator Process Production Program Development Property Published Comment Rattus Relative (related person)Reporting Research Research Personnel Research Proposals Resistance Safety Science Screening procedure Selection Criteria Sexual Transmission Sexually Transmitted Diseases Site Source Students Suggestion System Techniques Technology Testing Therapeutic Index Tissues Toxic effect Toxicology Universities Update Vagina Vaginal Ring Viral Virus Virus Diseases Virus Replication Woman Work absorption analog anti-HIV microbicide antimicrobial antimicrobial peptide base cathelicidin cecropin A cost data sharing dermaseptin design drug development drug resistant virus fungus high throughput screening immunogenicity improved in vitro Assay in vivo inhibitor/antagonist innovation irritation magainin microbial microbicide natural antimicrobial nonhuman primate novel novel strategies particle prevent product development programs protein aminoacid sequence rectal microbicide research clinical testing response small molecule three dimensional structure tool transmission process

项目摘要

We hypothesize that novel anti-HIV and anti-STI topical microbicides based on natural antimicrobial peptides collected in the Antimicrobial Peptide Database developed by the co-PI's laboratory (http://aps.unmc.due/AP/main.html) can be discovered and improved through peptide engineering technology. During the R21 phase, we will methodically screen peptides from the database and define specific inhibitors of HIV and HSV-2 as well as broad based inhibitory peptides. These active agents will be further developed in order to understand their range and mechanism of anti-HIV action. Superior peptides identified in SA1 will be characterized in SA2 to provide a rationale for continued development in SA3 using various molecular strategies which will result in the improvement of the therapeutic index of the peptide agents, with and without other small molecule microbicides, in order to begin development of an effective microbicide product. This product will be formulated and evaluated in animal models and safety assessment studies in the R33 portion of the project. Our goal is to produce a female controlled preventative agent which can be utilized to prevent the sexual transmission of viral, bacterial and fungal organisms with a focus on inhibiting the transmission of HIV. The research data will be entered into the existing antimicrobial peptide database to facilitate the use by funding agencies, other researchers, students and the public.

我们假设，基于共同 PI 实验室开发的抗菌肽数据库 (http://aps.unmc.due/AP/main.html) 中收集的天然抗菌肽，可以开发出新型抗 HIV 和抗 STI 局部杀菌剂。通过肽工程技术发现并改进。在 R21 阶段，我们将从数据库中系统地筛选肽，并定义 HIV 和 HSV-2 的特定抑制剂以及广泛的抑制肽。这些活性剂将得到进一步开发，以了解它们的抗艾滋病毒作用范围和机制。 SA1 中鉴定出的优质肽将在 SA2 中进行表征，为 SA3 中使用各种分子策略的持续开发提供理论依据，这将导致肽制剂的治疗指数得到改善，无论有或没有其他小分子杀微生物剂，以便开始开发有效的杀菌剂产品。该产品将在该项目 R33 部分的动物模型和安全评估研究中进行配制和评估。我们的目标是生产一种女性控制的预防剂，可用于预防病毒、细菌和真菌生物体的性传播，重点是抑制艾滋病毒的传播。研究数据将输入现有的抗菌肽数据库，以方便资助机构、其他研究人员、学生和公众使用。