De novo designed coiled coils as scaffolds for lanthanides, including novel imaging agents with a twist.

For much of their history, lanthanides were thought to be biologically inert. However, the last decade has seen the discovery and development of the field of native lanthanide biochemistry. Lanthanides exhibit a variety of interesting photophysical properties from which many useful applications derive. The development of effective functional lanthanide complexes requires control of their coordination sphere; something proteins manage very effectively through their 3D metal-binding sites. α-Helical coiled coil peptides are miniature scaffolds which can be designed de novo and can retain the favourable properties of larger proteins within a much simplified system. Metal binding sites, including those which bind lanthanides can be engineered into the coiled coil sequence. This review will highlight the opportunities presented by the use of coiled coil peptides as scaffolds for lanthanide binding and the potential to control the coordination environment by simple modifications to peptide sequence. Designed lanthanide coiled coils offer opportunities to gain greater insight into native lanthanide biochemistry as well as to develop new functional complexes, including imaging agents.

Unusual Magnetic Field Responsive Circularly Polarized Luminescence Probes with Highly Emissive Chiral Europium(III) Complexes.

Chirality is ubiquitous within biological systems where many of the roles and functions are still undetermined. Given this, there is a clear need to design and develop sensitive chiral optical probes that can function within a biological setting. Here we report the design and synthesis of magnetically responsive Circularly Polarized Luminescence (CPL) complexes displaying exceptional photophysical properties (quantum yield up to 31 % and |glum | up to 0.240) by introducing chiral substituents onto the macrocyclic scaffolds. Magnetic CPL responses are observed in these chiral EuIII complexes, promoting an exciting development to the field of magneto-optics. The |glum | of the 5 D0 → 7 F1 transition increases by 20 % from 0.222 (0 T) to 0.266 (1.4 T) displaying a linear relationship between the Δglum and the magnetic field strength. These EuIII complexes with magnetic CPL responses, provides potential development to be used in CPL imaging applications due to improved sensitivity and resolution.

Recent Advances in the Synthesis of Peptoid Macrocycles.

Over the past two decades, developing medical applications for peptides has, and continues to be a highly active area of research. At present there are over 60 peptide-based drugs on the market and more than 140 in various stages of clinical trials. The interest in peptide-based therapeutics arises from their biocompatibility and their ability to form defined secondary and tertiary structures, resulting in a high selectivity for complex targets. However, there are significant challenges associated with the development of peptide-based therapeutics, namely peptides are readily metabolised in vivo. Peptoids are an emerging class of peptidomimetic and they offer an alternative to peptides. Peptoids are comprised of N-substituted glycines where side-chains are located on the nitrogen atom of the amide backbone rather than the α-carbon as is the case in peptides. This change in structure confers a high degree of resistance to proteolytic degradation but the absence of any backbone hydrogen bonding means that peptoids exhibit a high degree of conformational flexibility. Cyclisation has been explored as one possible route to rigidify peptoid structures, making them more selective, and, therefore more desirable as potential therapeutics. This review outlines the various strategies that have been developed over the last decade to access new types of macrocyclic peptoids.