Membrane-Acting Lytic Peptides

膜作用裂解肽

基本信息

批准号：
7318289
负责人：
JUN F LIANG
金额：
$ 21.77万
依托单位：
STEVENS INSTITUTE OF TECHNOLOGY
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：
2007-07-01 至 2011-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7318289
关键词：
Active Biological Transport Affect Aftercare Antibiotic Resistance Antibiotics Antineoplastic Agents Apoptosis Arginine Bacteria Binding Biological Assay Blood Circulation Cancer Patient Cause of Death Cell Survival Cell membrane Cells Condition Cytolysis Diffusion Disease Drug Delivery Systems Drug Efflux Drug Transport Drug resistance Drug-sensitive Enzymes Exposure to Extracellular Space Failure Heart Diseases In Vitro Infection Intracellular Transport Isotonic Exercise Lipid Bilayers Longevity Lysine Lytic Malignant Neoplasms Membrane Modeling Names Normal Cell Normal tissue morphology Nosocomial Infections Organ P-Glycoprotein P-Glycoproteins Peptides Pharmaceutical Preparations Pharmacotherapy Production Proteins Pump Rate Relapse Research Resistance Screening procedure Signal Transduction Site Sodium Chloride Solutions Stroke Structure Time Today Transmembrane Transport United States abstracting antimicrobial peptide cell killing chemotherapy concept cytotoxicity design disorder control efflux pump improved in vivo interstitial killings membrane activity neoplastic cell novel pressure residence success tumor

项目摘要

DESCRIPTION (provided by applicant): Membrane-Acting Lytic Peptides Abstract Membrane-acting peptides (lytic peptides) are a group of cationic peptides which have their primary target site on the cell membrane and can kill cells by causing cell lysis. Because of the action site of lytic peptides is the cell membrane, they are effective to drug resistance cells, and can kill drug sensitive and resistant cells indiscriminately. This unique character makes lytic peptides become very attractive for their potential applications in the treatment of drug resistance related diseases. However, real application of lytic peptides as dugs is being hindered by their extremely low stability and selectivity. In this proposal, we propose to develop novel membrane-acting lytic peptides with high stability and selectivity. Smart lytic peptides have the potential to be used as drugs in the treatment of various drug resistance related diseases including cancer and infections. Two specific aims of this project are to: i) design and synthesize novel membrane-acting lytic peptides; ii) evaluate the stability, selectivity, and cell lysis activity of these membrane-acting lytic peptides in vitro and in vivo. Membrane-Acting Lytic Peptides Narrative Widespread drug resistance poses a significant problem and is responsible for the failure of chemotherapy in common diseases including cancers and various infections. In this application, we propose to introduce drug delivery concept into lytic peptide design to develop novel lytic peptides with high stability and selectivity. The success of this project may greatly improve the treatment of drug resistance related diseases such as cancer, infections, and infection associated diseases.

描述（由申请人提供）：膜作用裂解肽抽象膜作用肽（裂解肽）是一组阳离子肽，它们在细胞膜上具有主要靶位点，可以通过引起细胞裂解来杀死细胞。由于裂解肽的作用位点是细胞膜，因此它们对耐药细胞有效，并且可以杀死药物敏感和抗性细胞。这种独特的特征使裂解肽在治疗耐药性相关疾病中的潜在应用中变得非常有吸引力。但是，裂解肽作为DUG的实际应用受到其极低的稳定性和选择性的阻碍。在此提案中，我们建议开发具有高稳定性和选择性的新型膜作用裂解肽。智能裂解肽有可能用作药物，以治疗各种耐药性疾病，包括癌症和感染。该项目的两个具体目的是：i）设计和合成新型膜作用的裂解肽； ii）评估这些膜作用裂解肽在体外和体内的稳定性，选择性和细胞裂解活性。膜作用裂解肽的叙事广泛的耐药性构成了一个重大问题，并导致了包括癌症和各种感染在内的常见疾病中化学疗法的失败。在此应用中，我们建议将药物递送概念引入裂解肽设计中，以开发具有高稳定性和选择性的新型裂解肽。该项目的成功可能会大大改善与耐药性相关疾病（例如癌症，感染和感染相关疾病）的治疗。