COCAINE ANALOG PEPTIDES FROM ANTI IDIOTYPIC ANTIBODIES

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，努力寻找有效的治疗方法 可卡因成瘾一直没有成功。多巴胺的研究近况 Transporter(DAT)提供了不同位置的有力证据 多巴胺转位和可卡因结合。鉴于这种认识， 识别阻断可卡因与可卡因结合的药理物质的策略 但DAT不像可卡因那样有效地抑制多巴胺的摄取 出现了。我们提出了这样一种假设，即从 抗独特型(AB2β)抗体的抗原结合区 能够在不干扰的情况下抑制可卡因与DAT的结合 随着多巴胺的吸收，应该起到治疗“可卡因拮抗剂”的作用。在……里面 在这个项目中，我们将追求四个具体目标： 1.所选抗体2beta的Fab片段相对于其 DAT的结合亲和力和特异性 2.抗原结合单链抗体的克隆与表达 所选抗体2beta的区域 3.研究这些单链抗体阻断可卡因与 不干扰多巴胺摄取的DAT 4.序列数据分析

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