Design and construction of diverse synthetic peptide and polypeptide libraries

Abstract

The present invention concerns the design and construction of diverse peptide and polypeptide libraries. In particular, the invention concerns methods of analytical database design for creating datasets using multiple relevant parameters as filters, and methods for generating sequence diversity by directed multisyntheses oligonucleotide synthesis. The present methods enable the reduction of large complex annotated databases to simpler datasets of related sequences, based upon relevant single or multiple key parameters that can be individually directly defined. The methods further enable the creation of diverse libraries based on this approach, using multisynthetic collections of discrete and degenerate oligonucleotides to capture the diverse collection of sequences, or portions thereof.

1 - 34 . (canceled) 
     
     
         35 . A method of producing a combinatorial library of peptide or polypeptide sequences, comprising introducing amino acid side-chain chemical diversity into said peptide or polypeptide sequences at two or more amino acid positions, using combinatorial oligonucleotide synthesis. 
     
     
         36 . The method of  claim 36  wherein said amino acid side-chain chemical diversity is designed to mimic naturally occurring diversity in said peptide or polypeptide sequences. 
     
     
         37 . The method of  claim 36  wherein said library is an antibody library 
     
     
         38 . The method of  claim 38  wherein said antibody library comprises antibody heavy chain variable domain sequences. 
     
     
         39 . The method of  claim 38  wherein said library comprises antibody light chain variable domain sequences. 
     
     
         40 . The method of  claim 38  wherein said library is a combinatorial single-chain variable fragment (scFv) library. 
     
     
         41 . The method of  claim 38  wherein said antibody library is a library of Fab, Fab′, or F(ab′) 2  fragments.