Synthetic antibody protein mimics of infliximab by molecular scaffolding on novel CycloTriVeratrilene (CTV) derivatives

Longin, O., Hezwani, M., van de Langemheen, H. and Liskamp, R. M.J. (2018) Synthetic antibody protein mimics of infliximab by molecular scaffolding on novel CycloTriVeratrilene (CTV) derivatives. Organic and Biomolecular Chemistry, 16(29), pp. 5254-5274. (doi: 10.1039/c8ob01104d) (PMID:29892733)

Abstract

Syntheses of novel semi-orthogonally protected CycloTriVeratrilene (CTV) analogues with enhanced water solubility, that is 3 and 4, derived from the previously described CTV scaffold derivative 2 are described here. These scaffolds 2–4 enabled a sequential introduction of three different complementarity determining region (CDR) mimics via Cu(I)-catalysed azide–alkyne cycloaddition towards medium-sized protein mimics denoted as “synthetic antibodies”. The highly optimised sequential introduction enabled selective attachment of three different CDR mimics in a one-pot fashion. This approach of obtaining synthetic antibodies, demonstrated by the synthesis of paratope mimics of monoclonal antibody infliximab (Remicade®), provided a facile access to a range of (highly) pre-organised molecules bearing three different (cyclic) peptide segments and may find a wide range of applications in the field of protein–protein interaction disruptors as well as in the development of synthetic vaccines or lectin mimics. The prepared synthetic antibodies were tested for their affinity towards tumour necrosis factor alpha using surface plasmon resonance and synthetic antibodies with micromolar affinities were uncovered.

• Item Type: Articles
• Keywords: Physical and theoretical chemistry, organic chemistry, biochemistry.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Liskamp, Professor Robert and Longin, Ond?ej and Hezwani, Dr Mohammed and Van De Langemheen, Mr Helmus
• Authors: Longin, O., Hezwani, M., van de Langemheen, H., and Liskamp, R. M.J.
• College/School: College of Science and Engineering > School of Chemistry
• Journal Name: Organic and Biomolecular Chemistry
• Publisher: Royal Society of Chemistry
• ISSN: 1477-0520
• ISSN (Online): 1477-0539
• Published Online: 05 June 2018
• Copyright Holders: Copyright © 2018 The Authors
• First Published: First published in Organic and Biomolecular Chemistry 16(29):5254-5274
• Publisher Policy: Reproduced under a Creative Commons License