Factorial chemical libraries

Abstract

A method and library for determining the sequence of monomers in a polymer which is complementary to a receptor. The method provides for formation of pooled (6) and separate (10, 12) products. Separate products are subjected only to subsequent pooled coupling steps. Each pooled product is subsequently divided for formation of pooled and separate products. The resulting polymer library includes groups of polymer products. A first group of products (42) is used to identify the monomer at a first location in a polymer that is complementary to a receptor. A second group of products (44) is used to identify the monomer at a second location in a polymer that is complementary to a receptor.

Description

BACKGROUND OF THE INVENTION [0001] The present invention relates to the field of polymer screening. More specifically, in one embodiment the invention provides an improved polymer library and method of using the library to identify a polymer sequence that is complementary to a receptor. [0002] Many assays are available for measuring the binding affinity of receptors and ligands, but the information which can be gained from such experiments is often limited by the number and type of ligands which are available. Small peptides are an exemplary system for exploring the relationship between structure and function in biology. When the twenty naturally occurring amino acids are condensed into peptides they form a wide variety of three-dimensional configurations, each resulting from a particular amino acid sequence and solvent condition. The number of possible pentapeptides of the 20 naturally occurring amino acids, for example, is 205 or 3.2 million different peptides. The likelihood that...

AI Technical Summary

Benefits of technology

This patent describes an improved method for creating a library of polymers and screening them to identify which ones bind to a specific receptor. The method involves using a series of coupling steps, where each monomer is individually attached to a substrate. The resulting library is efficient and can be used to identify the monomer sequence that binds to a receptor. The method also includes a technique for screening polymers using factoring. Overall, this patent provides a more efficient and effective way to screen polymers for their ability to bind to a receptor.

Problems solved by technology

Many assays are available for measuring the binding affinity of receptors and ligands, but the information which can be gained from such experiments is often limited by the number and type of ligands which are available.

Prior methods of preparing large numbers of different oligomers have been painstakingly slow when used at a scale sufficient to permit effective rational or random screening.

Using the Merrifield method, it is not economically practical to screen more than a few peptides in a day.

Similar problems are encountered in the screening of other polymers having a diverse basis set of monomers.

For example, various methods of oligonucleotide synthesis such as the phosphite-triester method and the phosphotrieseter method, described in Gait, “Oligonucleotide Synthesis,” IRL Press, (1990), incorporated herein by reference for all purposes, have similar limitations when it is desired to synthesize many diverse oligonucleotides for screening.

While meeting with some success, prior methods have also met with certain limitations.

Also, some prior methods have not produced the desired amount of diversity as efficiently as would be desired.

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