An Orthogonally Protected CycloTriVeratrylene (CTV) as a Highly Pre-organized Molecular Scaffold for Subsequent Ligation of Different Cyclic Peptides towards Protein Mimics

Publication date: Available online 18 May 2017
Source:Bioorganic & Medicinal Chemistry
Author(s): Ondřej Longin, Helmus van de Langemheen, Rob M.J. Liskamp
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^®) and provides a convenient access to a range of highly pre-organised 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.

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