Systematic evolution of ligands by exponential enrichment: Chemi-ESLEX

Abstract

This application provides methods for identifying nucleic acid ligands capable of covalently interacting with targets of interest. The nucleic acids can be associated with various functional units. The method also allows for the identification of nucleic acids that have facilitating activities as measured by their ability to facilitate formation of a covalent bond between the nucleic acid, including its associated functional unit, and its target.

We claim:  
     
         1 . A nucleic acid candidate mixture comprised of at least 10 9  single stranded nucleic acids, said nucleic acids comprised of a fixed nucleotide segment and a randomized nucleotide segment, wherein each nucleic acid in said candidate mixture comprises a chemically reactive functional unit.  
     
     
         2 . The nucleic acid candidate mixture of  claim 1  wherein said randomized nucleotide segment is comprised of a contiguous string of between 8 and 250 nucleotides.  
     
     
         3 . The nucleic acid candidate mixture of  claim 1  wherein said randomized nucleotide segment is comprised of a contiguous string of between 8 and 60 nucleotides.  
     
     
         4 . The nucleic acid candidate mixture of  claim 1  wherein said mixture contains at least about 10 14  nucleic acids.  
     
     
         5 . The nucleic acid candidate mixture of  claim 1  wherein said randomized nucleotide segment is flanked by fixed nucleotide segments.  
     
     
         6 . The nucleic acid candidate mixture of  claim 5  wherein said flanking fixed nucleotide segments are selected to aid in the amplification of selected nucleic acids.  
     
     
         7 . The nucleic acid candidate mixture of  claim 1  wherein said chemically reactive functional unit is selected to facilitate an interaction with a target.  
     
     
         8 . The nucleic acid candidate mixture of  claim 1  wherein said chemically reactive functional unit is selected from the group consisting of photoreactive groups, active site directed compounds and peptides.  
     
     
         9 . The candidate mixture of  claim 1  wherein said chemically reactive functional unit is attached to an oligonucleotide hybridized to said fixed region.