Fig. 1. Strategies for constructing vast small molecule–peptide hybrid libraries. (a) Split-pool library of Rapamycin-like hybrid macrocycles comprised of an optimised FKBP-binding domain fused with a tetrapeptide effector domain. For A15-34-8: X = NHCOCH₂, R¹ = Phenylalanine, R² = N-methyl-d-Phenylalanine, R³ = Proline, R⁴ = N-methyl-Leucine. (b) DNA encoded library bearing a structurally-defined cyclic peptide scaffold with three encoded small molecule diversification sites. (c) Phage-displayed peptide library functionalised with mannose, biotin or sulphonamide each encoded by a silent barcode. [X]₄ = randomised (NNK)₄ library.