Ester bond hydrolysis of membrane phospholipids by Phospholipase A2 and consequent release of fatty acids are the initiating steps of inflammation. It is proposed in this study that the inhibition of phospholipase A2 is one of the ways to control inflammation. Investigations are carried out to identify the mode of inhibition of phospholipase A2 by the n‐hexadecanoic acid. It may help in designing of specific inhibitors of phospholipase A2 as anti‐inflammatory agents. The enzyme kinetics study proved that n‐hexadecanoic acid inhibits phospholipase A2 in a competitive manner. It was identified from the crystal structure at 2.5 Å resolution that the position of n‐hexadecanoic acid is in the active site of the phospholipase A2. The binding constant and binding energy have also been calculated using Isothermal Titration Calorimetry. Also, the binding energy of n‐hexadecanoic acid to phospholipase A2 was calculated by in silico method and compared with known inhibitors. It may be concluded from the structural and kinetics studies that the fatty acid, n‐hexadecanoic acid, is an inhibitor of phospholipase A2, hence, an anti‐inflammatory compound. The inferences from the present study validate the rigorous use of medicated oils rich in n‐hexadecanoic acid for the treatment of rheumatic symptoms in the traditional medical system of India, Ayurveda.

Translation, the mRNA-templated synthesis of peptides by the ribosome, can be manipulated to incorporate variants of the 20 cognate amino acids. Such approaches for expanding the range of chemical entities that can be produced by the ribosome may accelerate the discovery of molecules that can perform functions for which poorly folded, short peptidic sequences are ill suited. Here, we show that the ribosome tolerates some artificial helical aromatic oligomers, so-called foldamers. Using a flexible tRNA-acylation ribozyme-flexizyme-foldamers were attached to tRNA, and the resulting acylated tRNAs were delivered to the ribosome to initiate the synthesis of non-cyclic and cyclic foldamer-peptide hybrid molecules. Passing through the ribosome exit tunnel requires the foldamers to unfold. Yet foldamers encode sufficient folding information to influence the peptide structure once translation is completed. We also show that in cyclic hybrids, the foldamer portion can fold into a helix and force the peptide segment to adopt a constrained and stretched conformation.

No abstract

Racemates increase the chances of crystallization by allowing molecular contacts to be formed in a greater number of ways. With the advent of protein synthesis, the production of protein racemates and racemic-protein crystallography are now possible. Curiously, racemic DNA crystallography had not been investigated despite the commercial availability of L- and D-deoxyribo-oligonucleotides. Here, we report a study into racemic DNA crystallography showing the strong propensity of racemic DNA mixtures to form racemic crystals. We describe racemic crystal structures of various DNA sequences and folded conformations, including duplexes, quadruplexes, and a four-way junction, showing that the advantages of racemic crystallography should extend to DNA.

Macrocyclic peptides are an important class of bioactive substances. When inserting an aromatic foldamer segment in a macrocyclic peptide, the strong folding propensity of the former may influence the conformation...

A systematic approach to endow aromatic molecular architectures with both crystal growth ability from, and solubility in, water.

Using commercial screens for crystallization of biomolecules and taking advantage of the use of racemic crystallography allowed the production of X-ray quality single crystals and the elucidation at 1.08 Å resolution of the solid state structure of a difficult target: the complex between glucopyranose and a water soluble macrocyclic receptor equipped with dendritic multianionic solubilizing chains.

Tight binding was observed between the C‐terminal cross section of aromatic oligoamide helices in aqueous solution, leading to the formation of discrete head‐to‐head dimers in slow exchange on the NMR timescale with the corresponding monomers. The nature and structure of the dimers was evidenced by 2D NOESY and DOSY spectroscopy, mass spectrometry and X‐ray crystallography. The binding interface involves a large hydrophobic aromatic surface and hydrogen bonding. Dimerization requires that helices have the same handedness and the presence of a C‐terminal carboxy function. The protonation state of the carboxy group plays a crucial role, resulting in pH dependence of the association. Dimerization is also influenced by neighboring side chains and can be programmed to selectively produce heteromeric aggregates.