Our design aims to form a divergent precursor for late-stage reshaping of readily available phage-displayed libraries that contain two cysteines to yield 3 types of macrocycles. We evaluated downstream reactivity of bis(bromomethyl)benzaldehyde (KYL) on model peptide SAKGGRCYEDC which incorporates a lysine (Lys) residue in close proximity to the Nterminus, along with residues with nucleophilic side chains (Asp, Glu, Arg, Tyr) (Figure ). Nterminal Serine was selected because many phage-displayed libraries produced in our lab contain N-terminal Serine, and a peptide homologue with N-terminal residue Alanine (AAKGGRCYEDC) was evaluated subsequently. As bromine and chlorine both have been employed as leaving groups in such reactions, we tested both linkers (2.1 mM) on model peptide SAKGGRCYEDC (0.7 mM) in Tris-base buffer (TB) pH 8.6 (Figure ). We observed a half-conversion time t1/2 of 40 min for Cl leaving group and 1 min for Br leaving group (Figure , Figure ). The extended reaction time might be less optimal for modification on phage libraries; hence, we selected Br as a leaving group for further optimizations and subsequent applications. The product of the reaction-a monocyclic peptide with aldehyde can be purified and stored as lyophilized powder and is stable in acidic stocked solutions. Departure from those conditions leads to intermolecular reactivity of aldehyde and N-terminus.