Binding of leucomycin and its derivatives to E. Coli ribosomes

Structure-activity relationships have been discussed for inhibition of [¹⁴C] erythromycin binding to Escherichia coli ribosomes by leucomycin and its acyl derivatives in the light of the Fujita-Ban de novo model. The group contributions of various substituents show that acylation at position 4″ of the mycarose moiety of leucomycin increases affinity for binding of leucomycins to ribosomes. It is also indicated that unlike at position 2' in mycaminose region a free hydroxyl at position 9 of the lactone ring is not important for binding to ribosomes.     

Linear free energy relationships implicate three modes of binding for fluoroaromatic inhibitors to a mutant of carbonic anhydrase II

[figure: see text] Linear free energy relationships between binding affinity and hydrophobicity for a library of fluoroaromatic inhibitors of F131V carbonic anhydrase II (CA) implicate three modes of interaction. X-ray crystal structures suggest that F131 interacts with fluoroaromatic inhibitors, while P202, on the opposite side of the active site cleft, serves as the site of the hydrophobic contact in the case of the F131V mutant. 2-Fluorinated compounds bind more tightly, perhaps due to the field effect of the nearby fluorine on the acidity of the amide proton.     

Mechano-optical behavior in poly (ethylene terephthalate)/poly (ether imide) blends

Mechano-optical behavior and related structural evolution during uniaxial stretching of melt miscible poly (ethylene terephthalate) (PET)/poly (ether imide) (PEI) blends were studied near their glass transition temperature using an instrumented machine that measures true stress, true strain and spectral birefringence simultaneously. Stretching from amorphous state, two distinct stress-optical regimes were observed at temperatures between T_g and T_cc (cold crystallization). Near T_g, a typical photoelastic behavior persists until a critical temperature above which temperature independent initial stress optical behavior is observed. At those temperatures above T_g, where glassy behavior is observed, decreasing stretching rate was also found to eliminate this glassy photo elastic regime leading to the observation of a linear initial stress optical behavior that becomes temperature independent as expected from linear stress optical rule. Increasing PEI concentration in the blends suppresses crystallizability and increases temperature at which initial elastic region disappears giving way to pure liquid behavior where linear stress optical behavior is observed. This is attributed to the increase and broadening of the glass transition temperature with the addition of noncrystallizable PEI. In PET/PEI blends, the stress-optical coefficient (SOC), determined in a linear stress optical regime, was found to increase linearly with the increase in PEI concentration.     

Modification of Kagan's amide for improved activity as Chiral Solvating Agent in enantiodiscrimination during NMR analysis

A modification is proposed in Kagan's amide in order to improve its ability to offer stronger hydrogen bonding and hence better ability to bind with substrates. Introduction of chlorine in the amide aromatic ring along with the two nitro groups, increases the acidic character of amide hydrogen and makes the hydrogen bond stronger, the concept is tested by making three derivatives of Kagan's amide and the effect is confirmed by nmr analysis. The modified chlorinated Kagan's amides were then tested as chiral solvating agents for detection of optical purity of several types of substrates where the supramolecular recognition is measured by in situ nmr analysis. Several guest molecules such as amide, sulfoxide, epoxy-keto, hydroxy acid, diacid and phosphoric acid were scanned for this study and its efficiency is further established by comparison with samples of known optical purity.     

Quantitative surface field analysis: learning causal models to predict ligand binding affinity and pose

We introduce the QuanSA method for inducing physically meaningful field-based models of ligand binding pockets based on structure-activity data alone. The method is closely related to the QMOD approach, substituting a learned scoring field for a pocket constructed of molecular fragments. The problem of mutual ligand alignment is addressed in a general way, and optimal model parameters and ligand poses are identified through multiple-instance machine learning. We provide algorithmic details along with performance results on sixteen structure-activity data sets covering many pharmaceutically relevant targets. In particular, we show how models initially induced from small data sets can extrapolatively identify potent new ligands with novel underlying scaffolds with very high specificity. Further, we show that combining predictions from QuanSA models with those from physics-based simulation approaches is synergistic. QuanSA predictions yield binding affinities, explicit estimates of ligand strain, associated ligand pose families, and estimates of structural novelty and confidence. The method is applicable for fine-grained lead optimization as well as potent new lead identification.     

Pyrene functionalized oxacalix[4]arene architecture as dual readout sensor for expeditious recognition of cyanide anion

A pyrene functionalized oxacalix[4]arene architecture (DPOC) was utilized as a fluorescence probe for selective recognition of cyanide ions. The receptor DPOC shows excellent selectivity towards cyanide ion with a red shift of 108 nm in absorption band along with a significant change in colour from light yellow to pink. The fluorescence titration experiments further confirm the lower limit of detection as 1.7µM with no significant influences of competing anions. ¹ H-NMR titration experiments support the deprotonation phenomena, as the -NH proton disappears upon successive addition of cyanide ions. The DFT calculation also indicates a certain increment of -NH bond length upon interaction with cyanide ions. The spectral properties as well as colour of DPOC-CN^? system may be reversed upon the addition of Ag⁺/ Cu²⁺ ions up to 5 consecutive cycles. Moreover, DPOC coated “test strips” were prepared for visual detection of cyanide ions.

     

Homology modelling and virtual screening to explore potent inhibitors for MAP2K3 protein

Structural Chemistry - MAP2K3 protein is mitogen-activated protein kinase belonging to the family of kinases involved in intracellular cell proliferation. The mammalian MAPK family that consists of...     

Effect of Molecular Interactions on Electron‐Transfer and Antioxidant Activity of Bis(alkanol)selenides: A Radiation Chemical Study

Understanding electron‐transfer processes is crucial for developing organoselenium compounds as antioxidants and anti‐inflammatory agents. To find new redox‐active selenium antioxidants, we have investigated one‐electron‐transfer reactions between hydroxyl (^.OH) radical and three bis(alkanol)selenides (SeROH) of varying alkyl chain length, using nanosecond pulse radiolysis. ^.OH radical reacts with SeROH to form radical adduct, which is converted primarily into a dimer radical cation (>Se∴Se<)⁺ and α‐{bis(hydroxyl alkyl)}‐selenomethine radical along with a minor quantity of an intramolecularly stabilized radical cation. Some of these radicals have been subsequently converted to their corresponding selenoxide, and formaldehyde. Estimated yield of these products showed alkyl chain length dependency and correlated well with their antioxidant ability. Quantum chemical calculations suggested that compounds that formed more stable (>Se∴Se<)⁺, produced higher selenoxide and lower formaldehyde. Comparing these results with those for sulfur analogues confirmed for the first time the distinctive role of selenium in making such compounds better antioxidants.