Method and apparatus for peptide synthesis and screening

Abstract

Method and apparatus for simple and rapid preparation of reusable, addressable surface-immobilized arrays of biomolecules (libraries) used for screening for interaction with any biologically significant target. A special plate having on its surface a plurality of discreet functionalized substrate areas, typically in arrays of 10.times.10 to 400.times.400, is provided for chemical synthesis or bonding thereon of desired families of biomolecules (e.g. peptides, DNA, RNA, oligosaccharides). In the case of peptides, such as hexapeptides, the resulting permanently hexapeptide-loaded plate is a reusable Addressable Synthetic Peptide Combinatorial Library (ASPCL), in which 1 to 3 (typically two) of the positions in the sequence are uniquely identified by the address location. Plate embodiments include substrates of physically bonded (e.g. glued) conventional particulate materials such as Pepsyn-K, or functionalizable films of linear or crosslinked polymers covalently attached to, or physically adhered to the plate surface. Spacer arm moieties may also be attached to the substrates. A unique multi-slot block assembly is used to prepare the ASPCLs. In library applications, for example determining peptides which bind to functional proteins (enzymes, receptors, antibodies), the substrate-bound peptides are assembled with several positions consisting of uniformly distributed equimolar mixtures of residues, and 2 separated or sequential positions uniquely identified by their spatial location on the substrate array, the 'address'. Following identification of the known residues giving the greatest affinity for the arrayed positions in the sequence, optimal binding for the complete peptide sequence is determined by an iterative process replacing formerly mixed positions with known AAs at unique addresses.