Andrew C. Try

Porphyrin analogues of Tröger's base: large chiral cavities with a bimetallic binding site

2-Amino-5,10,15,20-tetraarylporphyrins react with formaldehyde to give good yields of the corresponding octaaryl derivatives of the Trogers base analogue in which two porphyrins are covalently Jinked by a diazocine bridge; the X-ray crystal-structure of the bis(tetraphenylporphyrinato)dipalladium(II) derivative 6 reveals a concave chiral cavity with two metal ion binding sites suitable for ditopic interactions with guest molecules.

RESOLUTION OF A PORPHYRIN ANALOGUE OF TROGER'S BASE BY MAKING USE OF LIGAND BINDING AFFINITY DIFFERENCES OF THE ENANTIOMERS

Abstract The dizinc(II) bis-porphyrin Trogers base analogue 3 can be resolved on a moderate scale by chromatography over a mixed silica- l -histidine benzyl ester medium.

Synthesis of accurate distance models of the primary donor - primary acceptor pair of bacterial photosynthetic reaction centres

The synthesis of 4 and 9, in which two porphyrins are joined by a biquinoxalinyl bridge and by a quinoxaline Trogers base, respectively, provide systems which have interporphyrin centre-centre and edge-edge distances that very closely match those between the primary donor - primary acceptor tetrapyrrolic pair in bacterial photosynthetic reaction centres.

Rigid chiral carbocyclic clefts as building blocks for the construction of new supramolecular hosts

Abstract The synthesis and resolution of two chiral carbocyclic cleft molecules containing carbonyl groups on the periphery of the cavity are reported. These compounds are reminiscent of Trogers base but contain a smaller cleft and additional carbonyl (or alcohol) groups. X-ray crystal structures of the dibromo and dimethyl derivatives show that the dihedral angle between the two aromatic rings is 79° and 85° respectively. The dibromo derivative provides entry into new supramolecular hosts, via introduction of additional recognition groups into the cleft molecules.

Enantioselective recognition of histidine and lysine esters by porphyrin chiral clefts and detection of amino acid conformations in the bound state

Resolution of the bisporphyrin Trogers base analogue 1 affords homochiral clefts that tightly bind histidine esters in 80–86% e.e. and lysine benzyl ester in 48% e.e.; the histidine esters are bound in fixed conformations that can be readily detected by 1H NMR spectroscopy as a result of the large dispersion of proton resonances by the ring currents of the two porphyrins.

19F NMR in the measurement of binding affinities of chloroeremomycin to model bacterial cell-wall surfaces that mimic VanA and VanB resistance

BACKGROUNDnThe emergence of bacteria that are resistant to vancomycin, the drug of choice against methicillin-resistant Staphylococcus aureus, has made the study of the binding characteristics of glycopeptides to biologically relevant depsipeptides important. These depsipeptides, terminating in D-alanyl-D-lactate, mimic the cell-wall precursors of resistant bacteria.nnnRESULTSnThe use of 19F-labelled ligands in the study of the therapeutically important vancomycin series of antibiotics is demonstrated. The substantial simplification of spectra that occurs when such labelled ligands are employed is used in the measurement of binding affinities of depsipeptides to chloroeremomycin (CE). Large enhancements of binding affinities are found at a model bacterial cell-wall surface (constituted from depsipeptides that are anchored into vesicles) relative to those measured in free solution.nnnCONCLUSIONSnSurface-enhanced binding, previously shown for strongly dimerizing glycopeptide antibiotics to normal -D-alanyl-D-alanine-terminating cell-wall precursors, is now demonstrated for CE to the surface of models of VanA- and VanB-resistant bacteria. The effect of depsipeptide chain length is shown to be critically important in producing and maximizing this enhancement.

Cooperativity in ligand binding expressed at a model cell membrane by the vancomycin group antibiotics

Dimerisation or the use of a membrane anchor enhances the binding of the glycopeptide antibiotics at the surface of a model cell membrane.

Use of model cell membranes to demonstrate templated binding of vancomycin group antibiotics

In this paper we demonstrate the importance of binding geometry and dimerisation at the surface of model cell membranes in the mode of action of the clinically important glycopeptide antibiotics. This has been achieved through the use of model cell membranes (micelles and vesicles) to which cell wall analogues are anchored via a hydrophobic decanoyl chain. A number of –D-Ala-terminating cell wall analogues, ranging from two to six residues in length, have been used. Dipeptide, pentapeptide and hexapeptide display enhanced binding to the antibiotic at the model cell surface, but tripeptide and tetrapeptide do not. The possible implications of the observed binding geometries for bacterial systems are discussed.

Binding of a vancomycin group antibiotic to a cell wall analogue from vancomycin-resistant bacteria

Glycopeptide antibiotics bind to bacterial cell wall peptide analogues terminating in -L-Lys-D-Ala-D-Lac in a similar manner to that of cell-wall analogues terminating in -LLys-D-Ala-D-Ala.

Ligand‐Induced Dissociation of the Asymmetric Homodimer of Ristocetin A Monitored by 19F NMR Spectroscopy

The binding of a ligand to the asymmetric homodimer of ristocetin A gives rise to a substantial reduction in dimerisation constant. This reduction is due to a higher binding affinity of ligand for monomer than for average dimer. The process can be clearly and usefully monitored by 19F NMR spectroscopy.