Encoded self-assembling chemical libraries.
The isolation of molecules capable of high-affinity and specific binding to biological targets is a central problem in chemistry, biology and pharmaceutical sciences. Here we describe the use of encoded self-assembling chemical (ESAC) libraries for the facile identification of molecules that bind macromolecular targets. ESAC technology uses libraries of organic molecules linked to individual oligonucleotides that mediate the self-assembly of the library and provide a code associated with each organic molecule. After panning ESAC libraries on the biomolecular target of interest, the 'binding code' of the selected compounds can be 'decoded' by a number of experimental techniques (e.g., hybridization on oligonucleotide microarrays). The potential of this technology was demonstrated by the affinity maturation (>40-fold) of binding molecules to human serum albumin and bovine carbonic anhydrase, leading to binders with dissociation constants in the nanomolar range.
Melkko
Samu
S
Department of Chemistry and Applied Biosciences, ETH Zürich, Winterthurerstrasse 190, CH-8057 Zürich, Switzerland.
Scheuermann
Jörg
J
Dumelin
Christoph E
CE
Neri
Dario
D
D000418:Albumins / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D002256:Carbonic Anhydrases / Q000378:metabolism*; D002417:Cattle; D017931:DNA Primers; D006801:Humans; D009841:Oligonucleotides / Q000378:metabolism*; D011485:Protein Binding
D000418:Albumins; D017931:DNA Primers; D009841:Oligonucleotides; D002256:Carbonic Anhydrases