Departure from bona fide library of random amino acid sequences and replacing them with built-in knowledge is not a new idea. Affinity maturation libraries built around previously discovered motifs are routinely used for optimization of peptide properties. Encoding the panintegrin binding RGD motif into phage libraries made it possible to accelerate binder discovery for specific types of integrins. Motifs do not always have to be peptidic: In genetically-encoded fragment based discovery, any fragments that have abilities to bind to a target can be incorporated into libraries. Another technique for constructing 'knowledge' is to introduce the population of AA sampled from a certain pool rather than completely randomization. For example, phage libraries that displayed short peptides sampled from human proteome simplified discovery of autoantibodies in humans. Interestingly, libraries with different built-in knowledge can still converge on the same results. Such convergent discovery, as observed in the selections of peptides that bind to O-GlcNac transferase (OGT): the same OGT-binding motif was found in randomized mRNA-displayed and phage displayed libraries, as well as a focused proteome derived library. Knowledge from 20 AA libraries has also been used indirectly to develop unnatural peptides. For example, Sulanemadlin-a 17 AA cyclic peptide with UAA and chemical 'stapling'-was developed from natural 12-mer peptide discovered via phage display 31 using a classical medicinal chemistry modification. All these examples point to the merits of transferring prior knowledge from natural peptide libraries into cPTM libraries for molecular discovery. We envisioned that such knowledge transfer can be facilitated using chemical linchpin that can yield divergent outcomes from the same peptide sequence.