Arris Pharmaceutical Corporation

Robert T Cass

Derek Hudson

Kevin R Shoemaker

Charles R Johnson

Lutz B Giebel

Michael J Ross

The invention relates to methods and systems of unhindered construction and display of tethered organic ligand molecules, and more particularly to preparation and use of thin film, substantially non-crosslinked hydrophilic polar multi-functionalized polymers (HPMPs) anchored to a variety of functionalized substrates so that the HPMP forms a thin film matrix layer providing a unique highly hydrated, high dielectric environment equivalent to an aqueous solution, for affinity binding of Ligands (L) to Tagged Target Molecules (TTMs). Ligands, and especially MER.sub.n ligand libraries such as peptide libraries, are singly tethered to the HPMP by a 'permanent' strong covalent bond so that subsequent displacement of the TTM does not also displace the ligand from the HPMP, thereby making the HPMP tethered Ligand library reusable. The HPMP thin film is on the order of 200-2000 .ANG. thick, is highly accessible (to the TTMs), and permits flexible, 3-D display of the singly tethered ligands for free permeability therein of the TTMs for affinity binding. The 3-D nature of the HPMP film provides high amplification of display, and the open nature of the matrix permits rapid elution of excess TTMs and other molecules. Importantly, the HPMP matrix layer, while providing amplification is also non-masking, being essentially transparent to detection methods. The combination of the reuseability, amplification and non-masking properties results in a very significant, many-fold increase in sensitivity and speed of screening assays.

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San Mateo, CA, United States of America

Robert T Cass