An orthogonally protected CycloTriVeratrylene (CTV) as a highly pre-organized molecular scaffold for subsequent ligation of different cyclic peptides towards protein mimics

作者：Longin Ondrej; van de langemheen Helmus; Liskamp Rob M J^*

来源：Bioorganic & Medicinal Chemistry, 2017, 25(18): 5008-5015.

DOI：10.1016/j.bmc.2017.05.038

• Protein mimic
• Peptide cyclisation
• Orthogonal functionalization
• Molecular scaffold
• Synthetic antibody

The synthesis of a semi-orthogonally protected CycloTriVeratrilene (CTV) scaffold derivative as well as the sequential introduction of three different peptide loops onto this molecular scaffold via Cu(I)-catalyzed azide alkyne cycloaddition towards a medium-sized protein mimic is described. This approach for the construction of medium-sized protein mimics is illustrated by the synthesis of a paratope mimic of the monoclonal antibody Infliximab (Remicade (R)) and provides access to a range of highly pre-organized molecular constructs bearing three different peptide segments. This approach may find wide applications for development of protein-protein interaction disruptors as well as synthetic vaccines.

• 出版日期2017-9-15