SYNTHETIC PEPTIDE LIBRARIES FOR ANTIVIRAL DRUG DISCOVERY

用于抗病毒药物发现的合成肽库

• 批准号: 2072089
• 负责人: PATRICIA A WEBER
• 金额: $ 7.17万
• 依托单位: HOUGHTEN PHARMACEUTICALS, INC.
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-06-01 至 1995-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2072089
• 关键词: Herpesviridae disease; acyclovir; antiviral agents; drug interactions; drug screening /evaluation; herpes simplex virus 1; herpes simplex virus 2; high performance liquid chromatography; mass spectrometry; microorganism disease chemotherapy; peptide chemical synthesis; plaque assay; protein sequence; pyrimidine analog; synthetic peptide; thymidine; toxicology; virus replication

Infections with herpes simplex viruses type-1 and type-2 are a major health problem in the U.S. with over 500,000 new cases per year. New drugs to treat herpes infections are needed, particularly since the virus is known to develop resistance to nucleoside analogs. Peptides have been shown to block the entry of viruses into the host cell, the activity of essential viral encoded enzymes and potentially other processes in the life cycle of viruses. A Synthetic Peptide Combinatorial Library (SPCL) composed of over 52 million D-amino acid hexapeptides will be screened for antiviral activity against herpes simples virus type-1. This unique drug discovery approach utilizes an iterative selection process to identify individual defined peptides for further efficacy studies. When the 400 samples of a D-amino acid hexapeptide library were screened, 22% of the mixtures were found to be active. Preliminary experiments have revealed D-amino acid peptide mixtures which inhibit the virus after infection of the host cell. D-amino acid peptides are expected to resist proteolytic degradation more effectively and therefore to have greater efficacy in vivo as topically active antiviral therapeutic agents.

单纯疱疹病毒1型和2型感染是一种主要的 在美国，每年有超过50万的新病例。 新 需要治疗疱疹感染的药物，特别是因为病毒 已知会对核苷类似物产生抗性。 肽已经 显示阻止病毒进入宿主细胞， 必需的病毒编码的酶和潜在的其他过程， 病毒的生命周期 合成肽组合文库（SPCL） 由超过5200万个D-氨基酸六肽组成， 针对单纯疱疹病毒1型的抗病毒活性。 这种独特 药物发现方法利用迭代选择过程， 鉴定用于进一步功效研究的单独限定的肽。 当 对400个D-氨基酸六肽库样品进行筛选，22%的样品被筛选出具有相同的氨基酸序列， 的混合物被发现是活性的。 初步实验已经 揭示了D-氨基酸肽混合物，其抑制病毒后， 宿主细胞的感染。 D-氨基酸肽有望抵抗 蛋白水解降解更有效，因此具有更大的 作为局部活性抗病毒治疗剂的体内功效。