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Abstract
Grant Number: 2R44AI051944-02 PI Name: DOWER, WILLIAM J. PI Email: bdower@xenoport.com PI Title: Project Title: New Method of Transcytosis Pathway and Ligand Discovery Abstract: 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.
Thesaurus Terms:
bacterial virus, combinatorial chemistry, drug delivery system, gastrointestinal drug absorption, ligand, method development, peptide chemical synthesis, peptide library, transcytosis
boronic acid, drug discovery /isolation, folate, oral administration
Institution: XENOPORT, INC. 3410 CENTRAL EXPRESSWAY SANTA CLARA, CA 950510703 Fiscal Year: 2003 Department: Project Start: 01-APR-2002 Project End: 28-FEB-2005 ICD: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES IRG: ZRG1