Current Chemical Biology - Volume 10, Issue 2, 2016

The recently elucidated molecular structure of neuronal axons is based on a tubular sequence of adducin-capped actin rings connected by spectrin tetramers. It has been suggested that this structure is formed by supramolecular polymerization of repeating unimers based on spectrin tetramers bound to actin rings. The large number of spectrin molecules connected to each actin ring enormously increases the rigidity of the assembly and the degree of polymerization. During axonal growth, new unimers can dynamically polymerize and macroscopic dimensions are attained. Fundamental self-assembly mechanisms assist the growth of neuronal filaments and coexist with the complex biochemical machinery that assists the biosynthesis and maintenance of the in vivo system.

Among gastro-intestinal cancers, pancreatic cancer is the fourth leading cause of cancer-related death mainly due to late diagnosis. Although there is significant improvement in chemotherapy regimen but still five year survival rate is maximum 6%. Resistance offered by cancer stem cells towards the chemotherapeutic drug might be one solid reason behind this. Cancer stem cells (CSC), a subset of the heterogeneous cell population of a tumor are self-renewable and can differentiate into all types of cancer cells. Inhibition of CSC activity might be a good approach in treatment of cancer. Anti-cancer activities of several naturally occurring phytochemicals are well established. Plethora of evidences supports the protective role of phytochemicals in suppressing CSC acivity. Here in this review an attempt has been made to summarize the activity of phytochemicals like curcumin, resveratrol, quercetin, catechin etc. towards inhibiting CSCs in pancreatic cancer.

Background: Iron-deficiency anemia (IDA) is considered the most common nutrition deficiency worldwide, which results from inadequate iron supply for erythropoiesis. Current treatments have poor chemical stability, bioavailability and some side effects. Polysaccharides have a variety of bioactivities, while no reports focused on IDA treatment by Lachnum polysaccharide iron complex. Objective: The aim of this study was to develop a kind of Lachnum polysaccharide-iron complex, evaluate its physical properties and treatment for IDA. Method: Firstly, we prepared the Lachnum polysaccharide iron complex (LEP-1b-Fe) and verified it was chelated successfully by infrared spectroscopy. Then its iron content, in vitro dissolution test and reducibility were determined. At last, IDA mice were used to determine the therapeutic effect of Lachnum polysaccharide and its iron complex. Weight growth rate, food consumption, contents of red blood cell (RBC), hemoglobin (Hb) and serum iron (SI), total iron binding capacity (TIBC), kidney index and spleen index were tested. Results: Iron percentage content of LEP-1b-Fe was 17.04% with improved solubility and reducing power. Infrared spectroscopy showed the iron core in LEP-1b-Fe was polymerized β-FeOOH structure, and the interaction between Fe (III) and LEP-1b mainly took place on the hydroxyl groups. LEP-1b could significantly increase the weight growth rate and food consumption of IDA mice, reduce kidney index and effectively increase the content of RBC, Hb, SI and TIBC. LEP-1b-Fe with the same concentration had better therapeutic effect on IDA. Conclusion: LEP-1b-Fe is a kind of polysaccharide-iron complex with good therapeutic effect on IDA and improved physical properties.

Thermotolerant yeasts, Candida easanensis strain JK-8 secreted a β-glucosidase when grown in liquid media containing various carbon sources. The greatest enzyme activity was found in medium containing 1% cellobiose as a sole carbon source. An extracellular β-glucosidase was purified to homogeneity by anion exchange chromatography and hydrophobic interaction chromatography. The molecular weight (Mw) of the β-glucosidase was estimated to be 48 kDa by SDS-PAGE. The optimal activity was at pH 4.5-5.5 and 60°C. The purified enzyme was stable in the pH range of 4.0-6.0 and had a 2 h half life at 50°C. The presence of metal ions (Ca2+, Mn2+, Zn2+ and Cu2+), mercaptoethanol and EDTA at 5 and 10 mM positively influenced its activity. It showed high specific activity for p-nitrophenyl-β-glucopyranoside (p-β-NPG) and laminarin. The similar Vmax of 10 μmol min-1mg protein-1 was found in both p-β-NPG (Km value of 5 mM) and laminarin (Km value of 5 mg mL-1). The enzyme displayed high tolerance to glucose with a Ki of 1.3 M and it was tolerant in the presence of methanol and ethanol at concentration up to 15%.

Background: Forskolin, a polyhydroxylated labdone diterpene possesses various medicinal properties in the treatment of chronic diseases, in humans. The present study aimed to evaluate the interaction and binding affinity between forskolin and HSA by in silico method and spectral analysis. Methods: The in silico study for screening the interaction of forskolin with HSA protein was carried out using AutoDock Vina software. The evaluation and characterization of the HSA–forskolin complex formation was achieved by spectroscopic methods–UV absorption, HPLC and FTIR analysis. Results: The in silico studies revealed that forskolin mainly binds on site II A and III A of HSA, with binding score -7.4 kcal mol-1and formations of hydrogen bonds with amino acid residues Asn 295, Arg 218 and Pro 447. The UV spectral analysis revealed the λ max for forskolin at 210 nm, for HSA at 220 & 280 nm, and for HSA bound forskolin at 215 nm indicating the formation of HSA-forskolin complex. A new peak was observed at retention time 0.787 min by HPLC analysis. The Bmax was found to be at 34 ± 0.12 mg protein and Kd value was 5.3x10-11 ± 0.03 M indicating interaction of forskolin with HSA. The FTIR analysis demonstrated shifting of amide I groups from 1600, 1640 to 1596, 1636 cm−1 respectively further establishing the binding of forskolin to HSA. Conclusion: The study demonstrates the binding of forskolin to HSA and formation of HSA-forskolin complex. We further hypothesize the imperative role of HSA in the pharmacokinetics of forskolin.

Background: Mangroves are of great significance to numerous people living along tropical shorelines. Mangroves are a rich source of various components having medicinal values. Recently, biodiversity and conservation of mangroves have been globally recognized as one of the critical issue. Objective: It is necessary to study proteins isolated from different mangroves in detail at molecular level along with their taxonomical relationship. The goal of the present study is to use bioinformatics tools to understand evolutionary significance by constructing phylogenetic tree in order to address relationship between true, minor and associate mangroves. Methods: Maturase K (matK) protein sequences of various mangroves were retrieved from NCBI and used for multiple sequence alignment and phylogenetic analysis. Bioinformatics tools were used to understand evolutionary significance by constructing phylogenetic tree. Three-dimensional structures of matK proteins from mangrove species were constructed by homology modeling. Results: Our study indicates that matK proteins are conserved in all groups of mangroves. The residues like histidine and lysine observed in place of glutamine might play a crucial role to provide proper three-dimensional fold to matK proteins. Three-dimensional models of matK obtained from different mangroves showed structural homology to each other. The homology model of matK contains predominantly helices, sheets and loops. Analysis of taxonomical relationship of mangroves through phylogenetic, sequence alignment and structural studies may provide valuable alternative to explore biological role of mangrove plants. Conclusion: Thus, this study suggests that matK proteins could be a good candidate for plant systematics and DNA barcoding studies of mangrove species.

Background: Multiple Endocrine Neoplasia Type 1 is caused by mutation in MEN1 genes that leads to parathyroid adenoma, duodenopancreatic neuroendocrine tumors, and pituitary adenomas.It also initiator of benign Lipomas, angiiofibromas and carcinoid tumor of thymus and lungs. It also incorporated in many such as transcription regulation, apoptosis, cell cycle control and DNA damage repair mechanisms. Methodology: The following mutations i.e. P12L, L22R, E45K, G110E, F144V, I147F, G161D, C170R, E184D and V220M in MEN1 were selected that were already reported. By using bioinformatics approaches check single amino acid substitution either their effect on protein structure, function and stability. In this methodology MODELLER, Chimera, NetSurfP, SNAP, IUPred, Polyphen and CDD were used. Result: All the predicted structure were showing accuracy greater than 90%. Also checked that L22R, E45K, F144V, I147F, G161D, C170R and V220M mutation were present in helix of mutated model and P12L, G110E and E184D are present in coil region. In P12L, E184D and G110E, mutation in exposed amino and their relative surface accessibility were decreased. While in L22R, E45K, F114V, I147F, G161D, C170R and V220M were present in the form of buried amino acid and their relative surface accessibility increased. These prediction showing expected accuracy of 78%, 82%, and 96%, 63%, 78%, 78%, 96%, 93%, 87% and 78% respectively in functionality changes. In case of structural damaging all the mutation showing high damaging effect on their function but their disorder tendency were low. Conclusion: Our results have shown that missense mutations P12L, L22R, E45K, G110E, F144V, I147F, G161D, C170R, E184D and V220M have strong structural, conformational, Function and pathogenic but low tendency order. This research helpful for clinical work at MEN1 genes to find out which mutation is responsible for disease causing.