Amino acids and peptides. XXXIX. Analogues of oxytocin exerting protracted biological effects

1963 ◽  
Vol 28 (8) ◽  
pp. 2021-2030 ◽  
Author(s):  
K. Jošt ◽  
J. Rudinger ◽  
F. Šorm
Keyword(s):  
Amino Acids ◽  
Biological Effects

Vasopressin and oxytocin analogs with interchanged sequence of amino acids in positions 7 and 8. synthesis and biological effects

1981 ◽  
Vol 46 (9) ◽  
pp. 2136-2139 ◽  
Author(s):  
Ivo Bláha ◽  
Viktor Krchňák ◽  
Milan Zaoral
Keyword(s):  
Amino Acids ◽  
Solid Phase Synthesis ◽  
Solid Phase ◽  
Biological Effects ◽  
Free Flow ◽  
Protecting Groups ◽  
Pressor Effect ◽  
Phase Synthesis ◽  
Antidiuretic Effect

p-Toluenesulfonyl-S-benzylcysteinyl-tyrosyl-phenylalanyl-glutaminyl-asparaginyl-S-benzylcysteinyl-NG-p-toluenesulfanylarginyl-prolyl-glycineamide (I) and S-benzylcysteinyl-tyrosyl-isoleucyl-glutaminyl-asparaginyl-S-benzylcysteinyl-leucyl-prolyl-glycine amide (III) were prepared by solid phase synthesis. After removal of the protecting groups, closure of the disulfide ring, and purification by continuous free-flow electrophoresis [arginine7, proline8]vasopressin (II) and [leucine7, proline8]oxytocin (IV) were obtained. The antidiuretic effect of II is markedly higher than its pressor effect; IV possesses c. 6% of the uterotonic and c. 10% of the galactogogous effect of oxytocin.

scholarly journals Meroterpenoids: A Comprehensive Update Insight on Structural Diversity and Biology

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 957
Author(s):  
Mamona Nazir ◽  
Muhammad Saleem ◽  
Muhammad Imran Tousif ◽  
Muhammad Aijaz Anwar ◽  
Frank Surup ◽  
...  
Keyword(s):  
Amino Acids ◽  
Secondary Metabolites ◽  
Biological Effects ◽  
Structural Diversity ◽  
Chemical Diversity ◽  
Biosynthetic Pathways ◽  
Natural Sources ◽  
Hybrid Compounds ◽  
Anti Inflammatory

Meroterpenoids are secondary metabolites formed due to mixed biosynthetic pathways which are produced in part from a terpenoid co-substrate. These mixed biosynthetically hybrid compounds are widely produced by bacteria, algae, plants, and animals. Notably amazing chemical diversity is generated among meroterpenoids via a combination of terpenoid scaffolds with polyketides, alkaloids, phenols, and amino acids. This review deals with the isolation, chemical diversity, and biological effects of 452 new meroterpenoids reported from natural sources from January 2016 to December 2020. Most of the meroterpenoids possess antimicrobial, cytotoxic, antioxidant, anti-inflammatory, antiviral, enzyme inhibitory, and immunosupressive effects.

scholarly journals F-actin-dependent Translocation of the Rap1 GDP/GTP Exchange Factor RasGRP2

2004 ◽  
Vol 279 (19) ◽  
pp. 20435-20446 ◽  
Author(s):  
Mariía J. Caloca ◽  
José L. Zugaza ◽  
Miguel Vicente-Manzanares ◽  
Francisco Sánchez-Madrid ◽  
Xosé R. Bustelo
Keyword(s):  
Signal Transduction ◽  
Amino Acids ◽  
Subcellular Distribution ◽  
Actin Polymerization ◽  
Biological Effects ◽  
Actin Dynamics ◽  
Exchange Factor ◽  
Common Structure ◽  
Direct Association ◽  
P21 Activated Kinase

RasGRPs constitute a new group of diacylglycerol-dependent GDP/GTP exchange factors that activate Ras subfamily GTPases. Despite a common structure, Ras-GRPs diverge in their GTPase specificity, subcellular distribution, and downstream biological effects. The more divergent family member is RasGRP2, a Rap1-specific exchange factor with low affinity toward diacylglycerol. The regulation of RasGRP2 during signal transduction has remained elusive up to now. In this report, we show that the subcellular localization of Ras-GRP2 is highly dependent on actin dynamics. Thus, the induction of F-actin by cytoskeletal regulators such as Vav, Vav2, Dbl, and Rac1 leads to the shift of RasGRP2 from the cytosol to membrane ruffles and its co-localization with F-actin. Treatment of cells with cytoskeletal disrupting drugs abolishes this effect, leading to an abnormal localization of RasGRP2 in cytoplasmic clusters of actin. The use of Rac1 effector mutants indicates that the RasGRP2 translocation is linked exclusively to actin polymerization and is independent of other pathways such as p21-activated kinase JNK, or superoxide production. Biochemical experiments demonstrate that the translocation of RasGRP2 to membrane ruffles is mediated by the direct association of this protein with F-actin, a property contained within its 150 first amino acids. Finally, we show that the RasGRP2/F-actin interaction promotes the regionalized activation of Rap1 in juxtamembrane areas of the cell. These results reveal a novel function of the actin cytoskeleton in mediating the spatial activation of Ras subfamily GTPases through the selective recruitment of GDP/GTP exchange factors.

scholarly journals Natural and Synthetic Halogenated Amino Acids—Structural and Bioactive Features in Antimicrobial Peptides and Peptidomimetics

Molecules ◽  
2021 ◽  
Vol 26 (23) ◽  
pp. 7401
Author(s):  
Mario Mardirossian ◽  
Marina Rubini ◽  
Mauro F. A. Adamo ◽  
Marco Scocchi ◽  
Michele Saviano ◽  
...  
Keyword(s):  
Amino Acids ◽  
Antimicrobial Peptides ◽  
Mode Of Action ◽  
Biological Effects ◽  
3D Structure ◽  
Surface Characteristics ◽  
Antimicrobial Drugs ◽  
Antibiotic Resistant ◽  
Physico Chemical ◽  
Proteins And Peptides

The 3D structure and surface characteristics of proteins and peptides are crucial for interactions with receptors or ligands and can be modified to some extent to modulate their biological roles and pharmacological activities. The introduction of halogen atoms on the side-chains of amino acids is a powerful tool for effecting this type of tuning, influencing both the physico-chemical and structural properties of the modified polypeptides, helping to first dissect and then rationally modify features that affect their mode of action. This review provides examples of the influence of different types of halogenation in amino acids that replace native residues in proteins and peptides. Examples of synthetic strategies for obtaining halogenated amino acids are also provided, focusing on some representative compounds and their biological effects. The role of halogenation in native and designed antimicrobial peptides (AMPs) and their mimetics is then discussed. These are in the spotlight for the development of new antimicrobial drugs to counter the rise of antibiotic-resistant pathogens. AMPs represent an interesting model to study the role that natural halogenation has on their mode of action and also to understand how artificially halogenated residues can be used to rationally modify and optimize AMPs for pharmaceutical purposes.

Designing novel teduglutide analogues with improved binding affinity: An in silico peptide engineering approach

2020 ◽  
Vol 16 ◽  
Author(s):  
Ali Akbar Alizadeh ◽  
Siavoush Dastmalchi
Keyword(s):  
Amino Acids ◽  
Short Bowel Syndrome ◽  
Biological Effects ◽  
Term Treatment ◽  
Receptor Interaction ◽  
Alanine Scanning Mutagenesis ◽  
Short Bowel ◽  
Novel Treatments ◽  
Long Term Treatment ◽  
Dynamics Simulations

Introduction: Short bowel syndrome (SBS) is a disabling condition which occurs following the loss of substantial portions of intestine leading to inadequate absorption of nutrients and fluids. Teduglutide is the only drug which has been FDA-approved for long-term treatment of SBS. This medicine exerts its biological effects through binding to the GLP-2 receptor. Methods: The current study aimed to use computational mutagenesis approaches to design novel potent analogues of teduglutide. To this end, the constructed teduglutide-GLP2R 3D model was subjected to the alanine scanning mutagenesis where ARG20, PHE22, ILE23, LEU26, ILE27 and LYS30 were identified as the key amino acids involved in ligand-receptor interaction. In order to design potent teduglutide analogues, using MAESTROweb machine learning method, the residues of teduglutide were virtually mutated into all naturally occurring amino acids and the affinity improving mutations were selected for further analysis using PDBePISA methodology which interactively investigates the interactions established at the interfaces of macromolecules. Result: The calculations resulted in D15I, D15L, D15M and N24M mutations which can improve the binding ability of ligand to receptor. Final evaluation of identified mutations was performed by molecular dynamics simulations indicating that D15I and D15M are the most reliable mutations to increase teduglutide affinity towards its receptor. Conclusion: The findings in the current study may facilitate designing more potent teduglutide analogues leading to the development of novel treatments in short bowel syndrome.

scholarly journals ‘Carbon-Monoxide-Releasing Molecule-2 (CORM-2)’ Is a Misnomer: Ruthenium Toxicity, Not CO Release, Accounts for Its Antimicrobial Effects

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 915
Author(s):  
Hannah M. Southam ◽  
Michael P. Williamson ◽  
Jonathan A. Chapman ◽  
Rhiannon L. Lyon ◽  
Clare R. Trevitt ◽  
...  
Keyword(s):  
Amino Acids ◽  
Carbon Monoxide ◽  
Mammalian Cells ◽  
Reduced Glutathione ◽  
Biological Effects ◽  
Significant Loss ◽  
Binding Affinities ◽  
Strong Negative Correlation ◽  
Inhibition Of Growth ◽  
Intracellular Target

Carbon monoxide (CO)-releasing molecules (CORMs) are used to deliver CO, a biological ‘gasotransmitter’, in biological chemistry and biomedicine. CORMs kill bacteria in culture and in animal models, but are reportedly benign towards mammalian cells. CORM-2 (tricarbonyldichlororuthenium(II) dimer, Ru2Cl4(CO)6), the first widely used and commercially available CORM, displays numerous pharmacological, biochemical and microbiological activities, generally attributed to CO release. Here, we investigate the basis of its potent antibacterial activity against Escherichia coli and demonstrate, using three globin CO sensors, that CORM-2 releases negligible CO (<0.1 mol CO per mol CORM-2). A strong negative correlation between viability and cellular ruthenium accumulation implies that ruthenium toxicity underlies biocidal activity. Exogenous amino acids and thiols (especially cysteine, glutathione and N-acetyl cysteine) protected bacteria against inhibition of growth by CORM-2. Bacteria treated with 30 μM CORM-2, with added cysteine and histidine, exhibited no significant loss of viability, but were killed in the absence of these amino acids. Their prevention of toxicity correlates with their CORM-2-binding affinities (Cys, Kd 3 μM; His, Kd 130 μM) as determined by 1H-NMR. Glutathione is proposed to be an important intracellular target of CORM-2, with CORM-2 having a much higher affinity for reduced glutathione (GSH) than oxidised glutathione (GSSG) (GSH, Kd 2 μM; GSSG, Kd 25,000 μM). The toxicity of low, but potent, levels (15 μM) of CORM-2 was accompanied by cell lysis, as judged by the release of cytoplasmic ATP pools. The biological effects of CORM-2 and related CORMs, and the design of biological experiments, must be re-examined in the light of these data.

Phosphorylation of Ser-80 of VP1 and Ser-254 of VP2 is essential for human BK virus propagation in tissue culture

2011 ◽  
Vol 92 (11) ◽  
pp. 2637-2645 ◽  
Author(s):  
Pei-Lain Chen ◽  
Pang-Hung Hsu ◽  
Chiung-Yao Fang ◽  
Chi-Fang Chang ◽  
Wei-Chih Ou ◽  
...  
Keyword(s):  
Amino Acids ◽  
Biological Effects ◽  
Vero Cells ◽  
Bk Virus ◽  
Site Directed Mutagenesis ◽  
Structural Proteins ◽  
Virus Propagation ◽  
Early Protein ◽  
Liquid Chromatography Tandem Mass

BK virus (BKV) infection may cause polyomavirus-associated nephropathy in patients with renal transplantation. Recently, the phosphorylated amino acids on the structural proteins VP1, VP2 and VP3 of BKV have been identified by liquid chromatography–tandem mass spectrometry in our laboratory. In this study, we further analysed the biological effects of these phosphorylation events. Phosphorylation of the BKV structural proteins was demonstrated by [32P]orthophosphate labelling in vivo. Site-directed mutagenesis was performed to replace all of the phosphorylated amino acids. The mutated BKV genomes were transfected into Vero cells for propagation analysis. The results showed that expression of the early protein LT and of the late protein VP1 by the mutants VP1-S80A, VP1-S80-133A, VP1-S80-327A, VP1-S80-133-327A and VP2-S254A was abolished. However, propagation of other mutants was similar to that of wild-type BKV. The results suggest that phosphorylation of Ser-80 of VP1 and Ser-254 of VP2 is crucial for BKV propagation.

scholarly journals A Possible Mechanism Underlying the Effectiveness of Acupuncture in the Treatment of Drug Addiction

2008 ◽  
Vol 5 (3) ◽  
pp. 257-266 ◽  
Author(s):  
Chae Ha Yang ◽  
Bong Hyo Lee ◽  
Sung Hoon Sohn
Keyword(s):  
Amino Acids ◽  
Drug Addiction ◽  
Dopamine Release ◽  
Biological Effects ◽  
Basic Mechanism ◽  
Dopamine Neurons ◽  
Brain Neurotransmitter ◽  
Reinforcing Effects ◽  
Abused Drugs ◽  
Behavioral Evidence

Clinical trials are currently underway to determine the effectiveness of acupuncture in the treatment of drug addiction. While there are still many unanswered questions about the basic mechanisms of acupuncture, some evidence exists to suggest that acupuncture can play an important role in reducing reinforcing effects of abused drugs. The purpose of this article is to critically review these data. The neurochemical and behavioral evidence showed that acupuncture's role in suppressing the reinforcing effects of abused drugs takes place by modulating mesolimbic dopamine neurons. Also, several brain neurotransmitter systems such as serotonin, opioid and amino acids including GABA have been implicated in the modulation of dopamine release by acupuncture. These results provided clear evidence for the biological effects of acupuncture that ultimately may help us to understand how acupuncture can be used to treat abused drugs. Additional research using animal models is of primary importance to understanding the basic mechanism underlying acupuncture's effectiveness in the treatment of drug addiction.

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