Miltefosine has antifungal properties and potential for development as a therapeutic for invasive fungal infections. However, its mode of action in fungi is poorly understood. We demonstrate that miltefosine is rapidly incorporated into yeast, where it penetrates the mitochondrial inner membrane, disrupting mitochondrial membrane potential and leading to an… (More)
An efficient strategy for the preparation of N-linked glycopeptides is described. The method relies on the use of side chain protecting groups on aspartic acid residues, namely the allyl and Dmab esters, which are orthogonal to those utilised in Fmoc-strategy SPPS. After peptide assembly these protecting groups were selectively removed and the resulting… (More)
OBJECTIVES Antifungal treatment of uncommon filamentous fungal infections is problematic. This study determined the in vitro susceptibility of miltefosine, as a single agent and in combination with posaconazole or voriconazole, against these pathogens. METHODS Susceptibility to miltefosine of 34 uncommon filamentous fungi was tested using CLSI broth… (More)
Fluoroquinolones are very important drugs in the clinical antibacterial arsenal; their success is principally due to their mode of action: the stabilisation of a gyrase-DNA intermediate (the cleavage complex), which triggers a chain of events leading to cell death. Microcin B17 (MccB17) is a modified peptide bacterial toxin that acts by a similar mode of… (More)
The first example of synchrotron X-ray fluorescence imaging of cultured mammalian cells in cyclic peptide research is reported. The study reports the first quantitative analysis of the incorporation of a bromine-labelled cyclic RGD peptide and its effects on the biodistribution of endogenous elements (for example, K and Cl) within individual tumor cells.
The transport of anions across cellular membranes is an important biological function governed by specialised proteins. In recent years, many small molecules have emerged that mimick the anion transport behaviour of these proteins, but only a few of these synthetic molecules also display the gating/switching behaviour seen in biological systems. A small… (More)
An efficient protocol for the chemoselective removal of Dmab esters on the solid phase is reported; this method has been successfully utilised for the convergent solid phase synthesis of N-linked glycopeptides.
A series of linear peptide based anion receptors, in which the distance between the bis[zinc(II)dipicolylamine] binding sites and the peptide backbone was varied systematically, was prepared and their anion binding ability was investigated using indicator displacement assays. Shortening the distance between the binding site and the peptide backbone was… (More)
Microcin B17 (MccB17) is a post-translationally modified peptide containing thiazole and oxazole heterocycles that interrupt the peptide backbone. MccB17 is capable of poisoning DNA gyrase through stabilization of the gyrase-DNA cleavage complex and has therefore attracted significant attention. Using a combination of Fmoc-strategy solid-phase peptide… (More)
A library of bis[zinc(II)dipicolylamine]-functionalised linear peptides was prepared using an efficient solid phase peptide synthesis approach and their use as chemosensors for anions in water was investigated using indicator displacement assays. High affinity and selectivity for pyrophosphate (PPi) over adenosine triphosphate (ATP) and adenosine… (More)