Random Structure Generation Combinatorial chemistry is well suited to studying peptides and oligonucleotides. Libraries of these compounds can be easily synthesized using solid-phase chemistry. Sequence degeneracy can be incorporated during the synthesis using either split synthesis or parallel synthesis. In the split synthesis approach, the solid support is divided into portions prior to each coupling step. A different synthon is then coupled to each portion.
All portions are recombined after coupling and the synthesis cycle is completed.
Oligonucleotide monomers on the other hand have similar reactivity. Degeneracy can be incorporated into oligonucleotides simply by using equimolar mixes of amidites at each coupling step. Of course, this variation does not yield one sequence per bead. In the parallel synthesis approach, different compounds are synthesized in multiple reaction vessels. Parallel synthesis has been performed using microtiter plates as well as in specific locations on solid surfaces that are reactive, such as the DNA chip technology developed by Affymetrix.