New Method of Transcytosis Pathway and Ligand Discovery

转胞吞途径和配体发现的新方法

• 批准号: 6711214
• 负责人: WILLIAM J DOWER
• 金额: $ 60.96万
• 依托单位: XENOPORT, INC.
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-04-01 至 2005-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6711214
• 关键词: bacterial virus; boronic acids; combinatorial chemistry; drug delivery systems; drug discovery /isolation; folate; gastrointestinal drug absorption; ligands; method development; oral administration; peptide chemical synthesis; peptide library; phage display; transcytosis

DESCRIPTION (provided by applicant): XenoPort will use NIH funding to develop a novel phage display method for identifying useful transcytotic pathways for oral administration of therapeutic drugs, and for identification of therapeutic molecules. Current methods for oral delivery of macromolecular and other drugs poorly absorbed by the intestine do not provide adequate oral bio-availability. Thus, new intestinal pathways to transport larger quantities of compound must be identified. Unfortunately, current methods of pathway identification are inadequate. XenoPort will address this problem by developing a new method for displaying synthetic molecules on phage particles to fully exploit the exquisite sensitivity and versatility of the phage for display of molecular libraries. These libraries will be used to screen for ligands to receptors directing the most active transcytosis pathways through the intestinal epithelium, enabling development of a commercial-ready technology platform adaptable to a wide variety of compounds in all therapeutic areas. Phase I studies established the fundamental method for constructing, screening and decoding libraries of synthetic compounds displayed on phage. Phase II will develop and evaluate a model peptide library of extraordinarily diverse synthetic compounds for enhanced discovery of novel ligands active in endocytosis and transcytosis. The technology will be commercialized via internal product development and strategic partnerships.

描述（由申请人提供）：XenoPort将使用NIH资金开发一种新型噬菌体展示方法，用于识别用于口服治疗药物的有用的胞吞途径，并用于识别治疗分子。目前用于口服递送大分子药物和其它难以被肠吸收的药物的方法不能提供足够的口服生物利用度。因此，必须确定新的肠道途径来运输更大量的化合物。不幸的是，目前的途径鉴定方法是不够的。XenoPort将通过开发一种在噬菌体颗粒上展示合成分子的新方法来解决这个问题，以充分利用噬菌体展示分子文库的灵敏度和多功能性。这些文库将用于筛选受体的配体，这些配体引导最活跃的转胞吞途径通过肠上皮，从而能够开发适用于所有治疗领域中各种化合物的商业化技术平台。第一阶段研究建立了构建、筛选和解码噬菌体展示的合成化合物文库的基本方法。第二阶段将开发和评估一个非常多样化的合成化合物的模型肽库，以增强发现内吞作用和转胞吞作用中具有活性的新型配体。该技术将通过内部产品开发和战略合作伙伴关系实现商业化。