Structure and conformation of peptides involving prolyl residue. IV. L-Prolyl-L-leucine monohydrate

The dipeptide, L-prolyl-L-leucine monohydrate (C11H20N2O3.H2O, molecular weight, 246.3) crystallizes in the monoclinic space group P2(1), with cell constants: a = 6.492(2)A, b = 5.417(8)A, c = 20.491(5)A, beta = 96.59(2) degrees, Z = 2, Do = 1.15 g/cm3, and Dc = 1.142 g/cm3. The structure was solved by SHELX-86 and refined by full matrix least squares methods to a final R-factor of 0.081 for 660 unique reflections (I greater than 2 sigma (I)) measured on an Enraf Nonius CAD-4 diffractometer (CuK alpha, lambda = 1.5418 A, T = 293 K). The peptide linkage exists in the trans conformation. The pyrrolidine ring exists in the envelope conformation. The values of the sidechain torsion angles are: chi 1 = -59.3(13) degrees, chi 21 = -63.1(16) degrees and chi 22 = 174.8(15) degrees for leucine (C-terminal). The crystal structure is stabilised by a three-dimensional network of N-H ... O, O-H ... O, and C-H ... O hydrogen bonds.     

Phylogeny of Acronychia (Rutaceae) and First Insights into Its Historical Biogeography and the Evolution of Fruit Characters

Background

The genus Acronychia (Citrus family, Rutaceae) contains 49 species of trees and shrubs that are found mainly in rain forest. The genus has a large distributional range from mainland southern Asia to Australia and New Caledonia, but most species are endemic to either New Guinea or Australia. This study aimed to provide the first detailed molecular phylogeny of Acronychia and use it to test the taxonomic value of fruit morphological characters, and infer the historical biogeography of the genus.

Methodology

Phylogenetic analyses (Bayesian Inference, Maximum Likelihood) were undertaken on nucleotide sequence data from two plastid (psbA-trnH, trnL-trnF) and three nuclear markers (ETS, ITS, NIAi3) from 29 Acronychia species (59% of the genus) and representatives of related genera.

Results and Conclusions

The results indicate that the South-East Asian genus Maclurodendron is nested phylogenetically within Acronychia and must be synonymized to render Acronychia monophyletic. Fruit morphological characters have been used previously to infer relationships within Acronychia and our analyses show that these characters are informative for some subclades but are homoplasious for the group as a whole. Apocarpous fruits are the ancestral state in Acronychia and subapocarpous and fully syncarpous fruits are derived. The unisexual flowers of Maclurodendron are derived from bisexual flowers, which are found in all species of Acronychia as well as its relatives. Acronychia probably first evolved on Australia with range expansion to New Guinea via stepping-stone dispersal or direct land connections within the Sahul Shelf, followed by two independent dispersals to areas west of New Guinea. Most species of Acronychia occur in either Australia or New Guinea, but no species occurs in both regions. This is surprising given the close proximity of the landmasses, but might be explained by ecological factors.     

Design and in silico modeling of Indoloquinoxaline incorporated keratin nanoparticles for modulation of glucose metabolism in 3T3-L1 adipocytes

The following study was done to assess the glucose utilizing efficiency of Indoloquinoxaline derivative incorporated keratin nanoparticles (NPs) in 3T3-L1 adipocytes. Indoloquinoxaline derivative had wide range of biological activities including antidiabetic activity. In this view, Indoloquinoxaline moiety containing N, N-dimethyl (3-fluoro-6H-indolo [3,2-b] quinoxalin-6-yl) methanamine compound was designed and synthesized, and further it is incorporated into keratin nanoparticles. The formulated NPs, drug entrapment efficiency, releasing capacity, stability, and physicochemical properties were characterized by various spectral analyzer and obtained results of characterizations were confirmed the properties of NPs. The analysis of mechanism underlying the glucose utilization of NPs was examined through molecular docking with identified target, and observed in silico study reports shown strong interaction of NPs in the binding pockets of AMPK and PTP1B. Based on the in silico screening, the formulated NPs was performed for in vitro cellular viability and glucose uptake studies on 3T3-L1 adipocytes. Interestingly, 40 μg of NPs displayed 78.2 ± 2.76% cellular viability, and no cell death was observed at lower concentrations. Further, the concentration dependent glucose utilization was observed at different concentrations of NPs in 3T3-L1 adipocytes. The results of NPs (40 μg) on glucose utilization have revealed eminent result 58.56 ± 4.54% compared to that of Metformin (10 μM) and Insulin (10 μM). The identified results clearly indicated that Indoloquinoxaline derivative incorporated keratin NPs significantly increased glucose utilization efficiency and protect the cells against the insulin resistance.     

Relevance of Non-ceruloplasmin Copper to Oxidative Stress in Patients with Hepatocellular Carcinoma

Altered copper homeostasis and oxidative stress have been observed in patients with hepatocellular carcinoma. Non-ceruloplasmin copper, the free form, is a potent pro-oxidant than the protein bound copper. The aim of the present study was to evaluate which form of copper can be correlated with the oxidative stress in the circulation and in the malignant liver tissues of hepatocellular carcinoma patients. Hepatocellular carcinoma patients (grades II and III, n = 18) were enrolled in this study. Serum levels of total, free and bound copper, ceruloplasmin, iron, iron-binding capacity, lipid peroxidation products, and enzymatic and non-enzymatic antioxidants were quantified in serum and in malignant liver tissues and compared with those of normal samples (n = 20). A significant positive correlation between the serum non-ceruloplasmin copper and lipid peroxidation products and negative correlation with antioxidants were observed in hepatocellular carcinoma patients. In liver tissue, glutathione peroxidase, superoxide dismutase, and catalase activity were significantly decreased with concomitant elevation in oxidative stress markers. Our experiment revealed that the elevation in non-ceruloplasmin copper has high relevance with the oxidative stress than the bound copper.     

A docking model of human ribonucleotide reductase with flavin and phenosafranine

Ribonucleotide Reductase (RNR) is an enzyme responsible for the reduction of ribonucleotides to their corresponding Deoxyribonucleotides (DNA), which is a building block for DNA replication and repair mechanisms. The key role of RNR in DNA synthesis and control in cell growth has made this an important target for anticancer therapy. Increased RNR activity has been associated with malignant transformation and tumor cell growth. In recent years, several RNR inhibitors, including Triapine, Gemcitabine and GTI-2040, have entered the clinical trials. Our current work focuses on an attempted to dock this inhibitors Flavin and Phenosafranine to curtail the action of human RNR2. The docked inhibitor Flavin and Phenosafranine binds at the active site with THR176, which are essential for free radical formation. The inhibitor must be a radical scavenger to destroy the tyrosyl radical or iron metal scavenger. The iron or radical site of R2 protein can react with one-electron reductants, whereby the tyrosyl radical is converted to a normal tyrosine residue. However, compounds such as Flavin and Phenosafranine were used in most of the cases to reduce the radical activity. The docking study was performed for the crystal structure of human RNR with the radical scavengers Flavin and Phenosafranine to inhibit the human RNR2. This helps to understand the functional aspects and also aids in the development of novel inhibitors for the human RNR2.