TY - JOUR ID - 393 TI - Multicomponent functionalization of the octreotide peptide macrocyclic scaffold JO - Eur. J. Org. Chem. PY - 2022 SP - e202200687 AU - Vasco, A. V. AU - Ceballos, L. G. AU - Wessjohann, L. A. AU - Rivera, D. G. AU - VL - 2022 UR - https://doi.org/10.1002/ejoc.202200687 DO - 10.1002/ejoc.202200687 AB - The replacement of the disulfide bridge by other types of side chain linkages has been a continuous endeavor in the development of cyclic peptide drugs with improved metabolic stability. Octreotide is a potent and selective somatostatin analog that has been used as an anticancer agent, in radiolabeled conjugates for the localization of tumors and as targeting moiety in peptide-drug conjugates. Here, we describe an onresin methodology based on a multicomponent macrocyclization that enables the substitution of the disulfide bond by a tertiary lactam bridge functionalized with a variety of exocyclic moieties, including lipids, fluorophores, and charged groups. Conformational analysis in comparison with octreotide provides key information on the type of functionalization permitting the conformational mimicry of the bioactive peptide. A2 - C1 - Bioorganic Chemistry ER -