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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(申请人提供)：膜作用裂解肽摘要膜作用肽(裂解肽)是一组阳离子多肽，其主要靶位在细胞膜上，可通过引起细胞裂解而杀死细胞。由于裂解肽的作用部位是细胞膜，因此对耐药细胞有效，可以不分青红皂白地杀灭药物敏感和耐药细胞。这种独特的性质使得裂解肽在治疗耐药相关疾病方面的潜在应用变得非常有吸引力。然而，裂解肽作为DUG的实际应用受到极低的稳定性和选择性的阻碍。在这项建议中，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。智能裂解肽有可能作为药物用于治疗包括癌症和感染在内的各种耐药相关疾病。本项目的两个具体目标是：i)设计和合成新型的膜作用裂解肽；ii)评价这些膜作用裂解肽的稳定性、选择性和细胞裂解活性。膜作用的裂解肽叙述广泛的耐药性是一个重要的问题，也是包括癌症和各种感染在内的常见疾病化疗失败的原因。在这一应用中，我们建议将药物释放的概念引入到裂解肽的设计中，以开发出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极大地改善抗药性相关疾病的治疗，如癌症、感染和感染相关疾病。