The Medicinal Chemistry Collection
Mixing block copolymers and proteins is an easy way to encapsulate the charged payload in nanoparticles. The resulting polyion complex micelles – PIC micelles – are stable in aqueous solution while the protein is protected against degradation. This approach can be used to deliver therapeutic proteins, and also to stabilise enzymes.
Ring-closing metathesis (RCM) and copper(i)-catalyzed azide–alkyne cycloaddition (CuAAC) are powerful strategies to introducing a macrocycle. This review focusses on the current synthetic approaches to access biologically active macrocycles that target important therapeutic aims for conditions such as cancer, cataracts, HIV, and neurological diseases.
Cyclotides are a group of cysteine-rich peptides derived from plants. Their exceptional stability based on their head-to-tail cyclized backbone and cystine knot, together with their tolerance to sequence modifications, make them promising drug design scaffolds into which novel bioactive sequences may be grafted. These grafting applications are achievable by solid-phase peptide synthesis. This article describes recent developments in the chemical synthesis and enzyme-mediated cyclization of cyclotides.
Lasso peptides contain a unique 3-D topography (known as a lariat knot) and are touted as novel scaffolds for biomedical applications. The synthesis of the non-threaded lasso peptide lassomycin was accomplished by solid-phase peptide chemistry and a novel way to install the C-terminal ester on the fully unprotected peptide.
The introduction of an iterative ‘click’ step into solid phase peptide synthesis protocols provides a method for rapid functionalisation of peptide side chains with a range of diverse moieties.
Aplytandiene-3 and six new metabolites with ‘gracilin’-type carbon skeletons are isolated from Goniobranchus splendidus. The structure of gracilin G is revised and a C-6 configuration deduced by 1D and 2D NMR spectroscopy. Goniobranchus daphne yields a lactone with a rearranged spongionellin-type skeleton. Selected isolated metabolites are cytotoxic against a HeLa S3 cell line.
This article will discuss the history behind the uses of faecal material, particularly its role in medical diagnosis. Faecal proteomics and other omics technologies (proteogenomics) are reviewed, including studies on the microbiome, in order to understand, identify, and treat diseases of the gastrointestinal tract and assist the drive towards personalized medicine.
Over the past decade, a plethora of indole-based synthetic cannabinoids (SCs) have emerged with structures inspired by scientific literature. The latest generation of SCs frequently use bioisosteric fluorine-for-hydrogen replacement. This highlight explores the evolution of SCs to this latest generation of fluorinated SCs, where accumulating evidence indicates increased health concerns.
The bridged disulfide ring of the fungal metabolite gliotoxin presents both synthetic challenges and confers the molecule with a variety of interesting biological activities. This review summarises recent synthetic strategies used to insert the disulfide and polysulfide bridge across the diketopiperazine ring and describes the limited structure–activity data available for this class of molecule.
Native chemical ligation followed by desulfurization is a powerful strategy for the chemical synthesis of protein targets. This review focusses on the current synthetic approaches to access amino acid building blocks bearing suitably positioned β-, γ- or δ-thiol ligation auxiliaries that have greatly expanded the scope of the ligation–desulfurization manifold.
