OBIMAP (One-Bead Interchain Multipeptide Assembly Platform).

A significant advancement in Merrifield's classic solid-phase peptide synthesis (SPPS) that greatly expands the scope of accessible peptide structures is reported here. Building upon the one-bead, one-compound (OBOC) concept, this approach enables the simultaneous synthesis of multiple peptides on a single bead, followed by a novel solid-phase interchain assembly reaction to produce the final peptide product. This method, the one-bead interchain multipeptide assembly platform (OBIMAP), successfully generates diverse peptide architectures, including linear, cyclic, and bicyclic structuresranging from minimal cyclic dipeptides to small proteinsmany of which are inaccessible through conventional SPPS. OBIMAP demonstrates superior efficiency in both time and product purity compared to traditional methods. Crucially, it eliminates the need for solution-phase fragment condensation, a common but cumbersome step commonly used in synthesizing therapeutic peptides (30-60 amino acids). In addition to enhancing conventional SPPS methodologies, the OBIMAP enables access to novel classes of peptide architectures, including highly constrained peptides that were previously considered synthetically inaccessible.