In order to apply combinatorial chemistry for the synthesis of DNA-encoded chemical libraries, a Split-&-Pool approach was pursued. Initially a set  of unique DNA-oligonucleotides (n) each containing a specific coding sequence is chemically conjugated to a corresponding set of small organic molecules. Consequently, the oligonucleotide-conjugate compounds are mixed ("Pool") and divided ("Split") into a number of groups (m). In appropriate conditions a second set of building blocks (m) are coupled to the first one and a further oligonucleotide which is coding for the second modification is enzymatically introduced before mixing again. This “split-&-pool” steps can be iterated a number of times (r) increasing at each round the library size in a combinatorial manner (i.e. (n x m)). Alternatively, peptide nucleic acids have been used to encode libraries prepared by "split-&-pool" method. A benefit of PNA-encoding is that the chemistry can be performed by standard SPPS.