Poster Presentation 9th Modern Solid Phase Peptide Synthesis & Its Applications Symposium 2023

Lanthanide ions (Ln³⁺) are attractive tools for use in the structural analysis of proteins because they allow the use of multiple spectroscopic techniques including NMR, electron paramagnetic resonance and time-resolved luminescence spectroscopy experiments, to probe protein structure, function, and dynamics in solution.

Complexes formed using chiral 1,4,7,10-tetraazacyclododecane (cyclen) are attractive candidates for tagging proteins due to their strong metal complexation properties and a tendency to form complexes with Ln³⁺ ions (scheme 1). The introduction of chirality into these ligands is highly desirable for applications in NMR spectroscopy. Previously, chirality has been introduced to cyclen ligands through alkylation of the cyclen nitrogens.² However, an alternative approach to access chiral cyclen derivatives is via the reduction of cyclic tetra-peptides.

Although the cyclization of tetrapeptides is typically low, cyclic tetrapeptides may be prepared in good yield by the introduction of pseudoproline turn-inducers.³ This  will be exploited to generate a variety of functionalised chiral cyclen derivatives that will then be investigated to evaluate their use in imaging protein structure through a multifaceted spectroscopic approach.

Scheme 1. Reaction scheme for access to the peptide derived chiral cyclen scaffold.