Unfairly forgotten deconvolution methods of combinatorial libraries

• Deconvolution of OBOC libraries leads to a high number of false positives, and the biological effects of the molecules are partially shaded. • In the deconvolution of DNA encoded libraries, the encoding DNA oligomer may yield false positives and partially shadows the biological effects of the molecules. • The Backsearch method uses different biological assays in which the effect of the free dissolved molecules is fully exerted. Since the introduction of split and pool synthesis, making it possible to create even billion-member combinatorial libraries, two deconvolution possibilities have been extensively used: the one-bead one-compound (OBOC) and the DNA-encoded methods. The originally available back search screening and the possibilities offered by the later-developed omission peptide libraries and the positional scanning have long been forgotten. Here, I compared the advantages and disadvantages of the above-mentioned methods, emphasizing the advantage of screening free dissolved molecules in the back search method.