COCAINE ANALOG PEPTIDES FROM ANTI IDIOTYPIC ANTIBODIES

来自抗独特型抗体的可卡因类似物肽

• 批准号: 6406174
• 负责人: MITCHELL HO
• 金额: $ 2.36万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-07-21 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6406174
• 关键词: analog; antiidiotype antibody; chemical binding; cocaine; dopamine; dopamine transporter; drug addiction antagonist; immunoglobulin structure; molecular cloning; neutralizing antibody; peptides; tissue /cell culture

DESCRIPTION: (Provided by Applicant) Cocaine addiction remains a major public health problem in industrialized countries. However, up till now, efforts to find effective therapies for cocaine addiction have been unsuccessful. Recent studies of the dopamine transporter (DAT) have provided strong evidence of differential sites for dopamine translocation and cocaine binding. In view of this knowledge, the strategy of identifying pharmacological agents that block cocaine binding to the DAT but do not inhibit dopamine uptake as effectively as cocaine has emerged. We have proposed the hypothesisthat peptides, generated from the antigen-combining regions of anti-idiotypic (Ab2 beta) antibodies and selected for their ability to inhibit cocaine binding to the DAT without interfering with dopamine uptake, should function as therapeutic "cocaine antagonists." In this project, we will pursue four specific aims: 1. Characterization of Fab fragments of selected Ab 2beta with respect to their binding affinity and specificity for the DAT 2. Generation of scFv by cloning and expression of the antigen-combining regions of the selected Ab 2beta 3. Investigation of the ability of these scFv to block cocaine binding to the DAT without interfering with dopamine uptake 4. Sequence data analysis

描述：（申请人提供） 可卡因成瘾仍然是工业化国家的一个主要公共卫生问题。 国家然而，到目前为止，寻找有效治疗方法的努力仍然不足。 可卡因成瘾一直没有成功。多巴胺的最新研究 转运蛋白（DAT）提供了强有力的证据， 多巴胺转运和可卡因结合。鉴于这一认识， 鉴定阻断可卡因与 DAT但不像可卡因那样有效地抑制多巴胺摄取 涌现我们提出了一个假设，即从蛋白质中产生的肽， 抗独特型（Ab2 β）抗体的抗原结合区，并选择 因为它们能够抑制可卡因与DAT结合而不干扰 与多巴胺的摄取，应该作为治疗“可卡因拮抗剂。“在 在这个项目中，我们将追求四个具体目标： 1.所选Ab 2 β的Fab片段的表征 DAT的结合亲和力和特异性 2.通过抗原结合的克隆和表达产生scFv 所选Ab 2 β的区域 3.研究这些scFv阻断可卡因结合至靶细胞的能力。 DAT不干扰多巴胺摄取 4.序列数据分析