Circular dichroism studies of low molecular weight hydrogelators: The use of SRCD and addressing practical issues.

Circular dichroism (CD) spectroscopy has been used extensively for the investigation of the conformation and configuration of chiral molecules, but its use for evaluating the mode of self-assembly in soft materials has been limited. Herein, we report a protocol for the study of such materials by electronic CD spectroscopy using commercial/benchtop instruments and synchrotron radiation (SR) using the B23 beamline available at Diamond Light Source. The use of the B23 beamtime for SRCD was advantageous because of the unique enhanced spatial resolution achieved because of its highly collimated and small beamlight cross section (ca.

Facet-Dependent Interactions of Islet Amyloid Polypeptide with Gold Nanoparticles: Implications for Fibril Formation and Peptide-Induced Lipid Membrane Disruption.

A comprehensive understanding of the mechanisms of interaction between proteins or peptides and nanomaterials is crucial for the development of nanomaterial-based diagnostics and therapeutics. In this work, we systematically explored the interactions between citrate-capped gold nanoparticles (AuNPs) and islet amyloid polypeptide (IAPP), a 37-amino acid peptide hormone co-secreted with insulin from the pancreatic islet. We utilized diffusion-ordered spectroscopy, isothermal titration calorimetry, localized surface plasmon resonance spectroscopy, gel electrophoresis, atomic force microscopy, transmission electron microscopy (TEM), and molecular dynamics (MD) simulations to systematically elucidate the underlying mechanism of the IAPP-AuNP interactions.

Effect of glucosamine HCl on dissolution and solid state behaviours of piroxicam upon milling.

Piroxicam is a non-steroidal anti-inflammatory drug that is characterised by low solubility and high permeability. In order to improve the drug dissolution rate, the co-grinding method was used as an approach to prepare piroxicam co-ground in the carriers such as glucosamine hydrochloride. As, this amino sugar (glucosamine HCl) has been shown to decrease pain and improve mobility in osteoarthritis in joints, therefore, the incorporation of glucosamine in piroxicam formulations would be expected to offer additional benefits to patients.

Cyclic α,β-peptoid octamers with differing side chain patterns: synthesis and conformational investigation.

The solution-phase synthesis and cyclisation of three α,β-peptoid octamers with differing side chain patterns is reported. One of these, compound C, showed a significantly greater resolution by NMR relative to the other two structurally related octamers. This observation was studied in detail by circular dichroism at a synchrotron light source to facilitate the correlation between the side chain patterns and conformational preference of these three peptoids.

C-3 branched δ-3,5-cis- and trans-THF sugar amino acids: synthesis of the first generation of branched homooligomers.

This article describes the efficient synthesis of the first generation of branched sugar amino acid (SAA) oligomers in solution phase via two main routes: by the use of a standard coupling reagent and via the use of active ester intermediates. Benzyl-protected dimeric carbopeptoid and methyl-protected dimeric and tetrameric, hexameric and octameric carbopeptoids were obtained from a branched δ-3,5-trans-tetrahydrofuran (THF) SAA and methyl-protected dimeric and tetrameric carbopeptoids were synthesised from a branched δ-3,5-cis-THF SAA. These systems are of interest because of their potential to display foldameric properties reminiscent of those observed in α-peptides and proteins.

Glucosamine HCl as a new carrier for improved dissolution behaviour: effect of grinding.

The co-grinding technique is one of the most effective methods for improving the dissolution rate of poorly water-soluble drugs and it is superior to other approaches from an economical as well as an environmental stand point, as the technique does not require any toxic organic solvents. The present work is an attempt to use d-glucosamine HCl (G-HCl) as a potential excipient to improve dissolution rate of carbamazepine (CBZ) from physical mixtures and co-grinding formulations. The effect of order of grinding on dissolution of CBZ was also investigated.

(3R,4R,5R)-5-(Acetamido-meth-yl)-N-benzyl-3,4-dihy-droxy-tetra-hydro-furan-3-carboxamide.

X-ray crystallographic analysis with Cu Kα radiation established the relative configurations of the stereogenic centers in the title compound, C(15)H(20)N(2)O(5), and clarified mechanistic ambiguities in the synthesis. The conformation of the five-membered ring approximates twisted, about a C-O bond. The absolute configuration of this carbon-branched dipeptide isostere was known based on the use of d-ribose as the starting material.

Penta-fluoro-phenyl (3R,4R,5S)-5-{[(3R,4R,5S)-5-azido-methyl-3,4-dimeth-oxy-2,3,4,5-tetra-hydro-furan-3-carboxamido]-meth-yl}-3,4-dimeth-oxy-2,3,4,5-tetra-hydro-furan-3-carboxyl-ate.

The title compound, C(22)H(25)F(5)N(4)O(9), is a stable penta-fluoro-phenyl ester inter-mediate in the synthesis of novel homo-oligomeric structures containing branched carbon chains. The structure is epimeric to the previously characterized dimeric penta-fluoro-phenyl ester with stereochemistry (3R,4R,5R), which was synthesized using d-ribose as starting material. The crystal structure of the title mol-ecule removes any ambiguities arising from the relative stereochemistries of the six chiral centres.

To enhance dissolution rate of poorly water-soluble drugs: glucosamine hydrochloride as a potential carrier in solid dispersion formulations.

The solid dispersion technique is the most effective method for improving the dissolution rate of poorly water-soluble drugs, however this is reliant on a suitable carrier and solvent being selected. The work presented explores D-glucosamine HCl (G-HCl) as a potential hydrophilic carrier to improve dissolution rate of a poorly water-soluble drug, carbamazepine (CBZ), from physical mixtures and solid dispersion formulations. The effect of different solvents in the preparation of solid dispersion formulations was also investigated.

Convenient solution-phase synthesis and conformational studies of novel linear and cyclic alpha,beta-alternating peptoids.

The synthesis of a novel family of peptidomimetics composed of linear and cyclic alpha,beta-alternating peptoids is described. Oligomers consisting of up to six peptoid residues (n = 1-3) were synthesized on large scale with use of an efficient iterative solution-phase method and longer oligomers (n = 4, 5) were obtained by the coupling of appropriately protected shorter oligomers. Preliminary conformational studies of these hybrid peptoids are reported.

Spectroscopic studies of oligomers containing 2,5-trans furanoid sugar amino acids.

Sugar amino acids and their oligomers, known as carbopeptoids, are commonly studied as foldamers. However, study of their conformational preference is often challenging when the adopted conformations are extended and/or disordered. This study is the first to explore the disordered nature of such carbopeptoids by utilizing a family of 2,5-trans carbopeptoids.

Classification of conformation for sugar amino acid systems using chiroptical spectroscopy.

A number of structurally related sugar amino acid systems have been examined by chiroptical methods to aid interpretation of their conformational preference. The use of circular dichroism, in addition to NMR and solution IR, has enabled classification of the conformations adopted by sugar amino acid systems as hydrogen-bonded regular, non-hydrogen-bonded regular, and non-hydrogen-bonded irregular. A set of tetrameric SAAs are examined and the effect of change in primary structure related to conformation.

Conformational studies of oligomeric oxetane-based dipeptide isosteres derived from L-rhamnose or D-xylose.

Conformational investigations have been undertaken on oligomers (dimers, tetramers, hexamers) of five closely related oxetane-based dipeptide isosteres. All the oligomers were subjected to a range of studies by NMR, FT-IR and CD spectroscopy. The oligomers derived from methyl 2,4-anhydro-5-azido-3-O-tert-butyldimethylsilyl-5-deoxy-L-rhamnonate 'monomer' all exhibited evidence of ordered conformations in chloroform and 2,2,2-trifluoroethanol (TFE) solution.

Circular dichroism studies of carbopeptoid-cyclodextrins.

A series of sugar amino acids, based on open chain sugars, have been oligomerised and cyclised. The resulting cyclic carbopeptoids have been examined for desirable properties such as host-guest chemistry (as in cyclodextrins) or self-assembling properties (e.g.

Helix-forming carbohydrate amino acids.

[reaction: see text] The solution-phase conformational properties of tetrameric and octameric chains of C-glycosyl alpha-d-lyxofuranose configured tetrahydrofuran amino acids (where the C-2 and C-5 substituents on the tetrahydrofuran ring are trans to each other) were examined using NMR and IR and CD in organic solvents. Studies by NMR and IR demonstrated that in chloroform solution, the tetramer 7 does not adopt a hydrogen-bonded conformation whereas the octamer 10 populates a well-defined helical secondary structure stabilized by 16-membered (i, i - 3) interresidue hydrogen bonds, similar to a pi-helix. Circular dichroism studies in trifluoroethanol are consistent with this conformation for the octamer 10, and also indicate that the tetramer 7 adopts a rigid conformation not stabilized by hydrogen bonds.

Tetrahydrofuran-based amino acids as library scaffolds.

A furanose sugar amino acid (SAA) has been utilized as a library scaffold for the first time. Two furanose SAA scaffolds were examined to illustrate their potential for derivatization. The resulting 99-member library contained three orthogonal points of diversification that allowed easy access to ethers and carbamates from a hydroxyl moiety, a range of ureas from an azide (via an amine), and a range of amides from a methyl ester.