Biologically active molecules

Master's thesis of Science "Investigation into the modulation of circadian clock proteins by dietary compounds and small molecules" is structured as follows: Chapter 1 Introduction; Chapter 2 Identification of novel bioactive compounds from Olea europaea by evaluation of chemical compounds in the OliveNetTM library: in silico bioactivity and molecular modelling, and in vitro validation of hERG activity; Chapter 3 Modulation of circadian core clock proteins by dietary compounds; Chapter 4 Molecular mechanisms of action of selected olive phenolics against epigenetic modifiers and the structur...

235p runthenight04 02-02-2023 5 3   Download

Natural products are currently underrepresented in the small-molecules drug library largely because of their extremely low yields, lower supply of natural resources and complex structures posing greater difficulty for structural modification and practical synthesis. Despite the challenges natural product based drugs continue to make impact in drug discovery.

223p spiritedaway36 26-11-2021 15 2   Download

Before we begin to study in detail the structure and activities of genes, and the experimental evidence underlying those concepts, we need a fuller outline of the adventure that lies before us. Thus, in this chapter and in chapter 3, we will fl esh out the brief history of molecular biology presented in chapter 1. In this chapter we will begin this task by considering the behavior of genes as molecules.

37p tangtuy05 30-03-2016 67 3   Download

Frog p26olf is a novel S100-like Ca21-binding protein found in olfactory cilia. It consists of two S100-like domains aligned sequentially, and has a total of four Ca21-binding sites (known as EF-hands). In this study, to elucidate the mechanism of Ca21-binding to each EF-hand (named EF-A, -B, -C and -D from the N-terminus of p26olf), we examined Ca21-binding in wild-type p26olf and also in its mutants in which a glutamate at the –z coordinate position within each Ca21-binding loop was substituted for a glutamine.

8p system191 01-06-2013 29 4   Download

Human interleukin-11 (hIL-11) is a pleiotropic cytokine that is involved in numerous biological activities such as hematopoiesis, osteoclastogenesis, neurogenesis and female fertility. IL-11 is obviously a key reagent to study the IL-11 receptors. However, conventional radio-iodination techni-ques lead to a loss of IL-11 bioactivity. Here, we report the construction and the production of a new recombinant human IL-11 (FPDIL-11). In this molecule, a speci®c phosphorylation site (RRASVA) has been introduced at the N-terminus of rhIL-11. ...

8p research12 29-04-2013 30 4   Download

In human neutrophils, both changes in intracellular Ca 2+ concentrations, [Ca 2+ ] i , and activation of phosphatidyl-inositol-3 kinase (PtdIns3K) have been proposed to play a role in regulating cellular function induced by chemoattr-actants. In this studywe have investigated the role of [Ca 2+ ] i and its effector molecule calmodulin in human neutrophils.

10p research12 23-04-2013 42 2   Download

Theoxidation-promotingreactivityof copper(II) complexof aminoglycosidic antibiotic amikacin [Cu(II)-Ami] in the presence of hydrogen peroxide, was studied at pH 7.4, using 2¢-deoxyguanosine (dG), pBR322 plasmid DNA and yeast tRNA Phe as target molecules. Themixtures of complexwith H2O2were found to be efficient oxidants, converting dG to its 8-oxo derivative, generating strand breaks in plasmid DNA and multiple cleavages in tRNA Phe .

10p tumor12 22-04-2013 35 3   Download

Earlier we presented several lines of evidence that a 67-kDa laminin binding protein (LBP) inLeishmania donovani,that is different from the putative mammalian 67-kDa laminin receptor, may play an important role in the onset of leish-maniasis, as these parasites invade macrophages in various organs after migrating through the extracellular matrix. Here we describe the membrane orientation of thisLeish-manialaminin receptor.

8p tumor12 20-04-2013 45 4   Download

The mitogen activated protein (MAP) kinase module: (Raf fiMEKfiERKs) is central to the control of cell growth, cell differentiation and cell survival. The fidelity of signalling and the spatio-temporal activation are key deter-minants in generating precise biological responses. The fidelity is ensured by scaffold proteins – protein kinase
insulators – andby specific docking sites. The duration and the intensity of the response are in part controlled by the compartmentalization of the signalling molecules. ...

9p tumor12 20-04-2013 30 2   Download

To elucidate the structural features of the mussel defensin MGD1 required for antimicrobial activity, we synthesized a series of peptides corresponding to the main known secon-dary structures of the molecule and evaluated their activity towards Gram-positive and Gram-negative bacteria, and filamentous fungi. We found that the nonapeptide corres-ponding to residues 25–33 of MGD1 (CGGWHRLRC) exhibited bacteriostatic activity once it was cyclized by a non-naturally occurring disulfide bridge.

9p fptmusic 16-04-2013 47 2   Download

We isolated a cholesterol-enriched membrane subpopulation from the so-called lipid raft fractions of Jurkat T-cells by taking advantage of its selective binding to a cholesterol-binding probe, BCh. The BCh-bound mem-brane subpopulation has a much higher cholesterol⁄phospholipid (C⁄P) molar ratio (
1.0) than the BCh-unbound population in raft fractions (
0.3). It contains not only the raft markers GM1 and flotillin, but also some T-cell receptor (TCR) signalling molecules, including Lck, Fyn and LAT. ...

10p fptmusic 12-04-2013 45 3   Download

The protein tyrosine phosphatase PTP-Basophil (PTP-Bas) and itsmouse homologue, PTP-Basophil-like (PTP-BL), are high molecular mass protein phosphatases consisting of a number of diverse protein–protein interaction modules. Several splicing variants of these phosphatases are known to exist thus demonstrating the complexity of these molecules. PTP-Bas/BL serves as a central scaffolding protein facilita-ting the assembly of a multiplicity of different proteins mainly via five different PDZ domains. ...

10p fptmusic 12-04-2013 36 2   Download

The transporter associated with antigen processing (TAP) delivers peptides into the lumen of the endoplasmic reticu-lum for binding onto major histocompatibility complex class I molecules. TAP comprises two polypeptides,TAP1 andTAP2,eachwithanN-terminal transmembranedomain and a C-terminal cytosolic nucleotide binding domain (NBD). The two NBDs have distinct intrinsic nucleotide binding properties.

16p fptmusic 12-04-2013 38 2   Download

Oxysterols, and particularly 7-ketocholesterol, appear to be strongly involved in the physiopathology of atherosclerosis. These molecules are suspected to be cytotoxic to the cells of the vascular wall and mono-cytes⁄macrophages, particularly by inducing apoptosis. Previous studies have demonstrated that 7-ketocholesterol-induced apoptosis is triggered by a sustained increase of cytosolic-free Ca 2+ , which elicits the mitochondrial pathway of apoptosis by activation of the calcium-dependent phosphatase calcineurin, leading to dephosphorylation of the ‘BH3 only’ protein BAD....

12p fptmusic 11-04-2013 33 2   Download

Numerous adhesion molecules have been described, and the molecular mechanisms of lymphocyte trafficking across the endothelium is starting to be elucidated. Identification of the molecules involved in the organoselec-tivity of this process would help in the targeting of drug therapy to specific tissues. Adhesion-regulating molecule-1 (ARM-1) is an adhesion-regulating molecule previously identified on T cells. It does not belong to any known families of adhesion molecules.

12p awards 06-04-2013 34 4   Download

Although of major impact in terms of biological and environmental haz-ards, interactions of actinide cations with biological molecules are only par-tially understood. Human serum transferrin (Tf) is one of the major iron carriers in charge of iron regulation in the cell cycle and consequently con-tamination by actinide cations is a critical issue of nuclear toxicology. Combined X-ray absorption spectroscopy (XAS) and near infrared absorp-tion spectrometry were used to characterize a new complex between Tf and Np (IV) with the synergistic nitrilotriacetic acid (NTA) anion....

0p awards 06-04-2013 49 3   Download

Cys34 in domain I of the three-domain serum protein albumin is the bind-ing site for a wide variety of biologically and clinically important small molecules, provides antioxidant activity, and constitutes the largest portion of free thiol in blood. Analysis of X-ray structures of albumin reveals that the loop containing Tyr84 occurs in multiple conformations. In structures where the loop is well defined, there appears to be an H-bond between the OH of Tyr84 and the sulfur of Cys34.

10p awards 05-04-2013 36 3   Download

The interaction between cell-adhesion molecules CD2 and CD58 is critical for an immune response. Modulation or inhibition of these interactions has been shown to be thera-peuticallyuseful. Synthetic 12-mer linear and cyclic peptides, and cyclic hexapeptides based on rat CD2 protein, were designed tomodulateCD2–CD58 interaction. The synthetic peptides effectively blocked the interaction between CD2– CD58 proteins as demonstrated by antibody binding, E-rosetting and heterotypic adhesion assays. ...

14p dell39 03-04-2013 50 3   Download

Gangliosideshavebeen found toreside inglycosphingolipid-enriched microdomains (GEM) of the plasma membrane and to be involved in the regulation of epidermal growth factor receptor (EGFr or ErbB1) activity.To gain further insight into the mechanisms involved in EGFr modulation by gangliosides, we investigated the distribution of EGFr family members in the plasma membrane of CHO-K1 cells, which were genetically modified to express different gan-glioside molecules or depleted of glycolipids.

10p dell39 03-04-2013 43 5   Download

The chemical structure of the free lipid A isolated from MesorhizobiumhuakuiiIFO15243 T was elucidated. Lipid A is a mixture of at least six species of molecules whose struc-tures differ both in the phosphorylation of sugar backbone and in fatty acylation. The backbone consists of ab(1¢fi6) linked 2,3-diamino-2,3-dideoxyglucose (DAG) disaccharide that is partly substituted by phosphate at position 4¢.The aglycon of the DAG-disaccharide has been identified as a-D-galacturonic acid.

13p dell39 03-04-2013 37 4   Download