Self-assembly of PNA-encoded peptides into microarrays

Several technologies have been described to immobilize libraries of small molecules or peptides in a microarray format. Herein, we describe protocols for an alternative strategy whereby each small molecule or peptide within a library is labeled with a peptide nucleic acid (PNA) tag such that they self-assemble in a microarray format upon hybridization with readily available DNA arrays. An important asset of the method is that it allows the library to be used in solution prior to hybridizing and as such offers the opportunity to separate the inhibitors bound to the protein from the rest of the library. Two methods based on size exclusion filtration or gel electrophoresis to separate protein-bound inhibitors from the remaining library are described.