scholarly journals Porous peptide frameworks generated by stacking non-self-complementary β-sheets

2014 ◽  
Vol 70 (a1) ◽  
pp. C562-C562
Author(s):  
Dmitriy Soldatov ◽  
Abdolreza Yazdani ◽  
Julia Crewson ◽  
Travis Fillion ◽  
Aaron Smith ◽  
...  
Keyword(s):  
Interlayer Space ◽  
Specific Property ◽  
Close Packing ◽  
Bioactive Molecules ◽  
Structural Motif ◽  
Supramolecular Polymers ◽  
Amino Acid Residues ◽  
Crystalline Materials ◽  
Wide Range ◽  
Β Sheet

"One of major approaches in the design of cavity space in the solids utilizes non-self-complementary molecules[1]. The irregular shape of the molecules and/or specific directionality of potential H-bonds prevent close packing of the molecules and yields various architectures hosting a second component, from inclusion compounds and co-crystals to complex non-crystalline patterns in biology. The strategy of non-self-complementary molecules has been extended in our studies to 2D supramolecular polymers based on short peptides[2]. The formation of the peptide layer with a desired overall geometry is controlled by strong, charge-assisted H-bonds (arrows in the Figure) in a β-sheet-like network as well as the segregation of hydrophobic amino acid residues into the interlayer space. The H-bonds add stability to the whole architecture while the hydrophobic groups keep the stacking layers at a distance that generates a cavity space available to a second component (encircled ""G"" in the Figure). A wide range of inclusions and co-crystals have been prepared in our group based on a series of dipeptides and higher peptide oligomers. For example, the incorporation of various organic solvents and bioactive molecules have been demonstrated for leucyl-alanine and similar dipeptides: alcohols, amides, phenols, pyridines, polyols, vitamins, scents and flavors. The crystal structure studies reveal a surprisingly persistent structural motif that can be used for engineering of crystalline materials with a specific property. We believe this type of peptide matrix may be utilized in the solid state organic synthesis [3] as reactive molecules of the second component can be oriented in a predictable way with respect to each other. "

Indium Bromide-catalyzed Unprecedented Hydrogenolysis: A Novel One-Pot Synthesis of Per-O-Acetylated β-carboxymethyl O and S-glycosides

2020 ◽  
Vol 24 (8) ◽  
pp. 900-908
Author(s):  
Ram Naresh Yadav ◽  
Amrendra K Singh ◽  
Bimal Banik
Keyword(s):  
Asymmetric Synthesis ◽  
Chiral Auxiliary ◽  
Bioactive Molecules ◽  
One Pot ◽  
Enantiomerically Pure ◽  
Stereoselective Glycosylation ◽  
One Pot Synthesis ◽  
Wide Range

Numerous O (oxa)- and S (thia)-glycosyl esters and their analogous glycosyl acids have been accomplished through stereoselective glycosylation of various peracetylated bromo sugar with benzyl glycolate using InBr3 as a glycosyl promotor followed by in situ hydrogenolysis of resulting glycosyl ester. A tandem glycosylating and hydrogenolytic activity of InBr3 has been successfully investigated in a one-pot procedure. The resulting synthetically valuable and virtually unexplored class of β-CMGL (glycosyl acids) could serve as an excellent potential chiral auxiliary in the asymmetric synthesis of a wide range of enantiomerically pure medicinally prevalent β-lactams and other bioactive molecules of diverse medicinal interest.

scholarly journals CRL4-DCAF12 Ubiquitin Ligase Controls MOV10 RNA Helicase during Spermatogenesis and T Cell Activation

2021 ◽  
Vol 22 (10) ◽  
pp. 5394
Author(s):  
Tomas Lidak ◽  
Nikol Baloghova ◽  
Vladimir Korinek ◽  
Radislav Sedlacek ◽  
Jana Balounova ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Activation ◽  
Ubiquitin Ligase ◽  
Cell Activation ◽  
Rna Helicase ◽  
Dependent Manner ◽  
Amino Acid Residues ◽  
Risc Complex ◽  
Wide Range

Multisubunit cullin-RING ubiquitin ligase 4 (CRL4)-DCAF12 recognizes the C-terminal degron containing acidic amino acid residues. However, its physiological roles and substrates are largely unknown. Purification of CRL4-DCAF12 complexes revealed a wide range of potential substrates, including MOV10, an “ancient” RNA-induced silencing complex (RISC) complex RNA helicase. We show that DCAF12 controls the MOV10 protein level via its C-terminal motif in a proteasome- and CRL-dependent manner. Next, we generated Dcaf12 knockout mice and demonstrated that the DCAF12-mediated degradation of MOV10 is conserved in mice and humans. Detailed analysis of Dcaf12-deficient mice revealed that their testes produce fewer mature sperms, phenotype accompanied by elevated MOV10 and imbalance in meiotic markers SCP3 and γ-H2AX. Additionally, the percentages of splenic CD4+ T and natural killer T (NKT) cell populations were significantly altered. In vitro, activated Dcaf12-deficient T cells displayed inappropriately stabilized MOV10 and increased levels of activated caspases. In summary, we identified MOV10 as a novel substrate of CRL4-DCAF12 and demonstrated the biological relevance of the DCAF12-MOV10 pathway in spermatogenesis and T cell activation.

scholarly journals Chemical Synthesis and NMR Solution Structure of Conotoxin GXIA from Conus geographus

Marine Drugs ◽  
2021 ◽  
Vol 19 (2) ◽  
pp. 60
Author(s):  
David A. Armstrong ◽  
Ai-Hua Jin ◽  
Nayara Braga Emidio ◽  
Richard J. Lewis ◽  
Paul F. Alewood ◽  
...  
Keyword(s):  
Solution Structure ◽  
3D Structure ◽  
Voltage Sensor ◽  
Solution Nmr ◽  
Striking Similarity ◽  
Amino Acid Peptide ◽  
Wide Range ◽  
Cone Snails ◽  
Drug Leads ◽  
Β Sheet

Conotoxins are disulfide-rich peptides found in the venom of cone snails. Due to their exquisite potency and high selectivity for a wide range of voltage and ligand gated ion channels they are attractive drug leads in neuropharmacology. Recently, cone snails were found to have the capability to rapidly switch between venom types with different proteome profiles in response to predatory or defensive stimuli. A novel conotoxin, GXIA (original name G117), belonging to the I3-subfamily was identified as the major component of the predatory venom of piscivorous Conus geographus. Using 2D solution NMR spectroscopy techniques, we resolved the 3D structure for GXIA, the first structure reported for the I3-subfamily and framework XI family. The 32 amino acid peptide is comprised of eight cysteine residues with the resultant disulfide connectivity forming an ICK+1 motif. With a triple stranded β-sheet, the GXIA backbone shows striking similarity to several tarantula toxins targeting the voltage sensor of voltage gated potassium and sodium channels. Supported by an amphipathic surface, the structural evidence suggests that GXIA is able to embed in the membrane and bind to the voltage sensor domain of a putative ion channel target.

scholarly journals Photocatalytic three-component asymmetric sulfonylation via direct C(sp3)-H functionalization

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Shi Cao ◽  
Wei Hong ◽  
Ziqi Ye ◽  
Lei Gong
Keyword(s):  
Asymmetric Catalysis ◽  
Organic Synthesis ◽  
Photochemical Reaction ◽  
Low Cost ◽  
Bioactive Molecules ◽  
Atom Economy ◽  
Mild Conditions ◽  
Wide Range ◽  
Unsaturated Carbonyl Compound ◽  
Direct Functionalization

AbstractThe direct and selective C(sp3)-H functionalization of cycloalkanes and alkanes is a highly useful process in organic synthesis owing to the low-cost starting materials, the high step and atom economy. Its application to asymmetric catalysis, however, has been scarcely explored. Herein, we disclose our effort toward this goal by incorporation of dual asymmetric photocatalysis by a chiral nickel catalyst and a commercially available organophotocatalyst with a radical relay strategy through sulfur dioxide insertion. Such design leads to the development of three-component asymmetric sulfonylation involving direct functionalization of cycloalkanes, alkanes, toluene derivatives or ethers. The photochemical reaction of a C(sp3)-H precursor, a SO2 surrogate and a common α,β-unsaturated carbonyl compound proceeds smoothly under mild conditions, delivering a wide range of biologically interesting α-C chiral sulfones with high regio- and enantioselectivity (>50 examples, up to >50:1 rr and 95% ee). This method is applicable to late-stage functionalization of bioactive molecules, and provides an appealing access to enantioenriched compounds starting from the abundant hydrocarbon compounds.

scholarly journals Recent Advancements in Polymer/Liposome Assembly for Drug Delivery: From Surface Modifications to Hybrid Vesicles

Polymers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1027
Author(s):  
Vincenzo De Leo ◽  
Francesco Milano ◽  
Angela Agostiano ◽  
Lucia Catucci
Keyword(s):  
Drug Delivery ◽  
First Generation ◽  
Phospholipid Bilayer ◽  
Bioactive Molecules ◽  
Systemic Delivery ◽  
Molecular Weights ◽  
Liposome Preparation ◽  
Wide Range ◽  
Liposome Surface

Liposomes are consolidated and attractive biomimetic nanocarriers widely used in the field of drug delivery. The structural versatility of liposomes has been exploited for the development of various carriers for the topical or systemic delivery of drugs and bioactive molecules, with the possibility of increasing their bioavailability and stability, and modulating and directing their release, while limiting the side effects at the same time. Nevertheless, first-generation vesicles suffer from some limitations including physical instability, short in vivo circulation lifetime, reduced payload, uncontrolled release properties, and low targeting abilities. Therefore, liposome preparation technology soon took advantage of the possibility of improving vesicle performance using both natural and synthetic polymers. Polymers can easily be synthesized in a controlled manner over a wide range of molecular weights and in a low dispersity range. Their properties are widely tunable and therefore allow the low chemical versatility typical of lipids to be overcome. Moreover, depending on their structure, polymers can be used to create a simple covering on the liposome surface or to intercalate in the phospholipid bilayer to give rise to real hybrid structures. This review illustrates the main strategies implemented in the field of polymer/liposome assembly for drug delivery, with a look at the most recent publications without neglecting basic concepts for a simple and complete understanding by the reader.

scholarly journals Mesoporous Silica Nanoparticles and Mesoporous Bioactive Glasses for Wound Management: From Skin Regeneration to Cancer Therapy

Materials ◽  
2021 ◽  
Vol 14 (12) ◽  
pp. 3337
Author(s):  
Sara Hooshmand ◽  
Sahar Mollazadeh ◽  
Negar Akrami ◽  
Mehrnoosh Ghanad ◽  
Ahmed El-Fiqi ◽  
...  
Keyword(s):  
Mesoporous Silica ◽  
Silica Nanoparticles ◽  
Mesoporous Silica Nanoparticles ◽  
Skin Regeneration ◽  
Bioactive Molecules ◽  
Wound Management ◽  
Bioactive Glasses ◽  
Wide Range

Exploring new therapies for managing skin wounds is under progress and, in this regard, mesoporous silica nanoparticles (MSNs) and mesoporous bioactive glasses (MBGs) offer great opportunities in treating acute, chronic, and malignant wounds. In general, therapeutic effectiveness of both MSNs and MBGs in different formulations (fine powder, fibers, composites etc.) has been proved over all the four stages of normal wound healing including hemostasis, inflammation, proliferation, and remodeling. The main merits of these porous substances can be summarized as their excellent biocompatibility and the ability of loading and delivering a wide range of both hydrophobic and hydrophilic bioactive molecules and chemicals. In addition, doping with inorganic elements (e.g., Cu, Ga, and Ta) into MSNs and MBGs structure is a feasible and practical approach to prepare customized materials for improved skin regeneration. Nowadays, MSNs and MBGs could be utilized in the concept of targeted therapy of skin malignancies (e.g., melanoma) by grafting of specific ligands. Since potential effects of various parameters including the chemical composition, particle size/morphology, textural properties, and surface chemistry should be comprehensively determined via cellular in vitro and in vivo assays, it seems still too early to draw a conclusion on ultimate efficacy of MSNs and MBGs in skin regeneration. In this regard, there are some concerns over the final fate of MSNs and MBGs in the wound site plus optimal dosages for achieving the best outcomes that deserve careful investigation in the future.

scholarly journals Phytochemicals and Antioxidant Activity in Oat-Buckwheat Dough and Cookies with Added Spices or Herbs

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2267
Author(s):  
Małgorzata Starowicz ◽  
Saruhan Arpaci ◽  
Joanna Topolska ◽  
Małgorzata Wronkowska
Keyword(s):  
Antioxidant Activity ◽  
Phenolic Content ◽  
Weight Basis ◽  
Bioactive Molecules ◽  
Total Phenolic ◽  
Antioxidant Power ◽  
Wide Range ◽  
Confectionery Products ◽  
Ferric Reducing Antioxidant Power ◽  
Phytochemical Contents

The aim of this study was to determine the phytochemicals and antioxidant activity in oat-buckwheat doughs and cookies with the addition of ten selected spices or herbs (2 g/100 g flours weight basis). The used spices and herbs, as was expected, showed a wide range of bioactive molecules, namely phenolic acids and flavonoids, and they are a rich source of components with antioxidant potential. All analysed oat-buckwheat dough showed higher antioxidant activity potential and higher total phenolic content (TPC) compared to cookies. The highest TPC was found in clove, both dough and cookies, with its addition showing the highest ferric reducing antioxidant power. Generally, cookies with the addition of spice/herbs showed higher phytochemical contents and antioxidant activity compared to oat-buckwheat cookies without the condiment. The technology of obtaining confectionery products, like oat-buckwheat cookies, that will favor the protection of bioactive compounds should still be improved.

Solid State Materials Chemistry

2021 ◽  
Author(s):  
Patrick M. Woodward ◽  
Pavel Karen ◽  
John S. O. Evans ◽  
Thomas Vogt
Keyword(s):  
Materials Science ◽  
Specific Property ◽  
Integrated Treatment ◽  
Synthesis Methods ◽  
Materials Chemistry ◽  
Wide Range ◽  
Hands On ◽  
Hands On Learning ◽  
Extended Solids ◽  
Core Concepts

This comprehensive textbook provides a modern, self-contained treatment for upper undergraduate and graduate level students. It emphasizes the links between structure, defects, bonding, and properties throughout, and provides an integrated treatment of a wide range of materials, including crystalline, amorphous, organic and nano- materials. Boxes on synthesis methods, characterization tools, and technological applications distil specific examples and support student understanding of materials and their design. The first six chapters cover the fundamentals of extended solids, while later chapters explore a specific property or class of material, building a coherent framework for students to master core concepts with confidence, and for instructors to easily tailor the coverage to fit their own single semester course. With mathematical details given only where they strengthen understanding, 400 original figures and over 330 problems for hands-on learning, this accessible textbook is ideal for courses in chemistry and materials science.

Probing structure–activity relationships in bactericidal peptide βpep-25

2008 ◽  
Vol 414 (1) ◽  
pp. 143-150 ◽  
Author(s):  
Ruud P. M. Dings ◽  
Judith R. Haseman ◽  
Kevin H. Mayo
Keyword(s):  
Amino Acid Residues ◽  
Neutralization Activity ◽  
Bacterial Membranes ◽  
E Coli ◽  
Structure Activity Relationships ◽  
Optimal Activity ◽  
Structure Activity ◽  
Cationic Residues ◽  
Β Sheet ◽  
And Staphylococcus Aureus

Cationic peptides, known to disrupt bacterial membranes, are being developed as promising agents for therapeutic intervention against infectious disease. In the present study, we investigate structure–activity relationships in the bacterial membrane disruptor βpep-25, a peptide 33-mer. For insight into which amino acid residues are functionally important, we synthesized alanine-scanning variants of βpep-25 and assessed their ability to kill bacteria (Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus) and to neutralize LPS (lipopolysaccharide). Activity profiles were found to vary with the bacterial strain examined. Specific cationic and smaller hydrophobic alkyl residues were crucial to optimal bactericidal activity against the Gram-negative bacteria, whereas larger hydrophobic and cationic residues mediated optimal activity against Gram-positive Staph. aureus. Lysine-substituted norleucine (n-butyl group) variants demonstrated that both charge and alkyl chain length mediate optimal activity. In terms of LPS neutralization, activity profiles were essentially the same against four species of LPS (E. coli 055 and 0111, Salmonella enterica serotype Typhimurium and Klebsiella pneumoniae), and different for two others (Ps. aeruginosa and Serratia marcescens), with specific hydrophobic, cationic and, surprisingly, anionic residues being functionally important. Furthermore, disulfide-bridged analogues demonstrated that an anti parallel β-sheet structure is the bioactive conformation of βpep-25 in terms of its bactericidal, but not LPS endotoxin neutralizing, activity. Moreover, βpep-25 variants, like the parent peptide, do not lyse eukaryotic cells. This research contributes to the development and design of novel antibiotics.

Lamellar mesoscopic organization of supramolecular polymers: a necessary pre-ordering secondary structure

2017 ◽  
Vol 8 (38) ◽  
pp. 5954-5961 ◽  
Author(s):  
J. Lacombe ◽  
C. Soulié-Ziakovic
Keyword(s):  
Secondary Structure ◽  
Supramolecular Polymers ◽  
Β Sheet

Thy-functionalized PPGs organize in lamellae due to the alignment of amide links in a β-sheet-like secondary structure analogous to proteins.

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