4,375 results match your criteria dimeric forms

Characterization of pendrin in urinary extracellular vesicles in a rat model of aldosterone excess and in human primary aldosteronism.

Hypertens Res 2021 Jul 29. Epub 2021 Jul 29.

Division of Nephrology, Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan.

Pendrin is a Cl/HCO exchanger selectively present in the intercalated cells of the kidney. Although experimental studies have demonstrated that pendrin regulates blood pressure downstream of the renin-angiotensin-aldosterone system, its role in human hypertension remains unclear. Here, we analyzed the quantitative changes in pendrin in urinary extracellular vesicles (uEVs) isolated from a total of 30 patients with primary aldosteronism (PA) and from a rat model of aldosterone excess. Read More

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Structural basis of the effect of activating mutations on the EGF receptor.

Elife 2021 Jul 28;10. Epub 2021 Jul 28.

Department of Chemistry, University College London, London, United Kingdom.

Mutations within the kinase domain of the epidermal growth factor receptor (EGFR) are common oncogenic driver events in non-small cell lung cancer. Although the activation of EGFR in normal cells is primarily driven by growth-factor-binding-induced dimerization, mutations on different exons of the kinase domain of the receptor have been found to affect the equilibrium between its active and inactive conformations giving rise to growth-factor-independent kinase activation. Using molecular dynamics simulations combined with enhanced sampling techniques, we compare here the conformational landscape of the monomers and homodimers of the wild-type and mutated forms of EGFR ΔELREA and L858R, as well as of two exon 20 insertions, D770-N771insNPG, and A763-Y764insFQEA. Read More

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Structural insights into the mechanism of human methyltransferase hPRMT4.

J Biomol Struct Dyn 2021 Jul 24:1-14. Epub 2021 Jul 24.

Translational Bioinformatics Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India.

Human PRMT4, also known as CARM1, is a type I arginine methyltransferase protein that catalyse the formation of asymmetrical dimethyl arginine product. Structural studies done to date on PRMT4 have shown that the N-terminal region, Rossmann fold and dimerization arm play an important role in PRMT4 activity. Elucidating the functions of these regions in catalysis remains to be explored. Read More

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Targeting SARS-CoV-2 main protease by teicoplanin: a mechanistic insight by docking, MM/GBSA and molecular dynamics simulation.

J Mol Struct 2021 Jul 18:131124. Epub 2021 Jul 18.

Department of Pharmaceutical Chemistry & Pharmacognosy, Unaizah College of Pharmacy, Qassim University, Saudi Arabia.

First emerged in late December 2019, the outbreak of novel severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) pandemic has instigated public-health emergency around the globe. Till date there is no specific therapeutic agent for this disease and hence, the world is craving to identify potential antiviral agents against SARS-CoV-2. The main protease (M) is considered as an attractive drug target for rational drug design against SARS-CoV-2 as it is known to play a crucial role in the viral replication and transcription. Read More

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Transient Tertiary Structures of Disordered Dynein Intermediate Chain Regulate its Interactions with Multiple Partners.

J Mol Biol 2021 Jul 14;433(18):167152. Epub 2021 Jul 14.

Department of Biochemistry and Biophysics, Oregon State University, Corvallis, OR 97331, United States. Electronic address:

The N-terminal domain of dynein intermediate chain (N-IC) is central to the cytoplasmic dynein 'cargo attachment subcomplex' and regulation of motor activity. It is a prototypical intrinsically disordered protein (IDP), serving as a primarily disordered polybivalent molecular scaffold for numerous binding partners, including three dimeric dynein light chains and coiled coil domains of dynein partners dynactin p150 and NudE. At the very N-terminus, a 40 amino acid single alpha helix (SAH) forms the major binding site for both p150 and NudE, while a shorter nascent helix (H2) separated from SAH by a disordered linker, is necessary for tight binding to dynactin p150 but not to NudE. Read More

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Activation of PKG restricts melanoma growth and invasion by interfering with the EGF/EGFR pathway.

J Invest Dermatol 2021 Jul 12. Epub 2021 Jul 12.

Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.

Drug resistance mechanisms still characterize metastatic melanoma, despite new treatments have been recently developed. Targeting of the cGMP/protein kinase G (PKG) pathway is emerging as a therapeutic approach in cancer research. In this study, we evaluated the anticancer effects of two polymeric linked dimeric (PDL) cGMP analogues able to bind and activate PKG, called PKG-activator (PA) 4 and 5. Read More

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Structures of substrate complexes of foamy viral protease-reverse transcriptase.

J Virol 2021 Jul 7:JVI0084821. Epub 2021 Jul 7.

Laboratory of Protein Structure, International Institute of Molecular and Cell Biology, Warsaw, Poland.

Reverse transcriptases (RTs) use their DNA polymerase and RNase H activities to catalyze the conversion of single-stranded RNA to double-stranded DNA, a crucial process for the replication of retroviruses. Foamy viruses (FV) possess a unique RT which is a fusion with the protease (PR) domain. The mechanism of substrate binding by this enzyme has been unknown. Read More

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Histidine Tautomerism Driving Human Islet Amyloid Polypeptide Aggregation in the Early Stages of Diabetes Mellitus Progression: Insight at the Atomistic Level.

Chem Asian J 2021 Jul 6. Epub 2021 Jul 6.

Department of Chemistry, Sungkyunkwan University, Suwon, 16419, South Korea.

Early oligomerization of human islet amyloid polypeptide (hIAPP), which is accountable for β-cell death, has been implicated in the progression of type 2 diabetes mellitus. Some researches have shown the connection between hIAPP and Alzheimer's disease as well. However, the mechanism of peptide accumulation and associated cytotoxicity remains unclear. Read More

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Symptom Severity, Infection Progression and Plant Responses in Solanum Plants Caused by Three Pospiviroids Vary with the Inoculation Procedure.

Int J Mol Sci 2021 Jun 8;22(12). Epub 2021 Jun 8.

Instituto de Biología Molecular y Celular de Plantas (IBMCP), Consejo Superior de Investigaciones Científicas (CSIC), Universitat Politècnica de València (UPV), Ciudad Politécnica de la Innovación (CPI) 8 E, Ingeniero Fausto Elio s/n, 46011 Valencia, Spain.

Infectious viroid clones consist of dimeric cDNAs used to generate transcripts which mimic the longer-than-unit replication intermediates. These transcripts can be either generated in vitro or produced in vivo by agro-inoculation. We have designed a new plasmid, which allows both inoculation methods, and we have compared them by infecting and with clones of (CEVd), (TCDVd), and (PSTVd). Read More

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Stability of p53 oligomers: Tetramerization of p53 impinges on its stability.

Biochimie 2021 Jun 28;189:99-107. Epub 2021 Jun 28.

School of Biology, Indian Institute of Science Education and Research Thiruvananthapuram, Thiruvananthapuram, 695551, Kerala, India. Electronic address:

The p53 protein has been known to exist structurally in three different forms inside the cells. Earlier studies have reported the predominance of the lower oligomeric forms of p53 over its tetrameric form inside the cells, although only the tetrameric p53 contributes to its transcriptional activity. However, it remains unclear the functional relevance of the existence of other p53 oligomers inside the cells. Read More

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Regulation of Dual Activity of Ascorbate Peroxidase 1 From by Conformational Changes and Posttranslational Modifications.

Front Plant Sci 2021 14;12:678111. Epub 2021 Jun 14.

Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup, South Korea.

Ascorbate peroxidase (APX) is an important reactive oxygen species (ROS)-scavenging enzyme, which catalyzes the removal of hydrogen peroxide (HO) to prevent oxidative damage. The peroxidase activity of APX is regulated by posttranslational modifications (PTMs), such as S-nitrosylation, tyrosine nitration, and S-sulfhydration. In addition, it has been recently reported that APX functions as a molecular chaperone, protecting rice against heat stress. Read More

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A Crystallographic Snapshot of SARS-CoV-2 Main Protease Maturation Process.

J Mol Biol 2021 Jun 24;433(18):167118. Epub 2021 Jun 24.

Institute of Physics of Sao Carlos, University of Sao Paulo, Av. Joao Dagnone, 1100, Jardim Santa Angelina, Sao Carlos 13563-120, Brazil. Electronic address:

SARS-CoV-2 is the causative agent of COVID-19. The dimeric form of the viral M is responsible for the cleavage of the viral polyprotein in 11 sites, including its own N and C-terminus. The lack of structural information for intermediary forms of M is a setback for the understanding its self-maturation process. Read More

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Aldose Reductase B1 in Pig Seminal Plasma: Identification, Localization in Reproductive Tissues, and Relationship With Quality and Sperm Preservation.

Front Cell Dev Biol 2021 8;9:683199. Epub 2021 Jun 8.

Department of Veterinary Medical Sciences, University of Bologna, Bologna, Italy.

Aldose reductase B1 (AKR1B1), a NADPH-dependent enzyme that belongs to the aldo-keto reductase protein superfamily, has been reported to be involved in both male and female reproductive physiology. The objectives of this study were: (1) to evaluate the concentration of SP-AKR1B1 in pig ejaculate fractions; (2) to describe the immunohistochemical localization of AKR1B1 alongside the boar genital tract; (3) to evaluate the relationship between SP-AKR1B1 and sperm quality/functionality parameters. Ejaculates from seven boars (one ejaculate per boar) were collected in separate portions [the first 10 mL of the sperm rich fraction (SRF-P1), the rest of the SRF (SRF-P2), and the post-SRF (PSRF)], and the concentration of SP-AKR1B1 was assessed using an enzyme-linked immunosorbent assay (ELISA). Read More

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DSC and FCS Studies Reveal the Mechanism of Thermal and Chemical Unfolding of CIA17, a Polydisperse Oligomeric Protein from .

J Phys Chem B 2021 Jul 24;125(26):7117-7127. Epub 2021 Jun 24.

School of Chemistry, University of Hyderabad, Hyderabad-500 046, India.

The mechanism of thermal and chemical unfolding of agglutinin (CIA17), a chitooligosacharide-specific phloem exudate lectin, was investigated by biophysical approaches. DSC studies revealed that the unfolding thermogram of CIA17 consists of three components ( ∼ 98, 106, and 109 °C), which could be attributed to the dissociation of protein oligomers into constituent dimers, dissociation of the dimers into monomers, and unfolding of the monomers. Intrinsic fluorescence studies on the chemical denaturation by guanidinium thiocyanate and guanidinium chloride indicated the presence of two distinct steps in the unfolding pathway, which could be assigned to dissociation of the dimeric protein into monomers and unfolding of the monomers. Read More

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Sphingosine kinase inhibition enhances dimerization of calreticulin at the cell surface in mitoxantrone-induced immunogenic cell death.

J Pharmacol Exp Ther 2021 Jun 22. Epub 2021 Jun 22.

Pharmacology, Penn State College of Medicine, United States

Agents that induce immunogenic cell death (ICD) alter the cellular localization of calreticulin (CRT) causing it to become cell surface exposed within the plasma membrane lipid raft microdomain (ectoCRT) where it serves as a damage associated molecular pattern that elicits an antitumor immune response. We have identified the sphingolipid metabolic pathway as an integral component of the process of ectoCRT exposure. Inhibition of the sphingosine kinases (SphKs) enhances mitoxantrone-induced production of hallmarks of ICD including ectoCRT production, with an absolute mean difference of 40 MFI (95% CI: 19 to 62; P=0. Read More

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Analysis of the DNA-binding properties of Alx1, an evolutionarily conserved regulator of skeletogenesis in echinoderms.

J Biol Chem 2021 Jul 19;297(1):100901. Epub 2021 Jun 19.

Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, Pennsylvania, USA. Electronic address:

Alx1, a homeodomain-containing transcription factor, is a highly conserved regulator of skeletogenesis in echinoderms. In sea urchins, Alx1 plays a central role in the differentiation of embryonic primary mesenchyme cells (PMCs) and positively regulates the transcription of most biomineralization genes expressed by these cells. The alx1 gene arose via duplication and acquired a skeletogenic function distinct from its paralog (alx4) through the exonization of a 41-amino acid motif (the D2 domain). Read More

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G-Quadruplex Formation by DNA Sequences Deficient in Guanines: Two Tetrad Parallel Quadruplexes Do Not Fold Intramolecularly.

Chemistry 2021 Jun 18. Epub 2021 Jun 18.

Institute of Biophysics of the Czech Academy of Sciences, Královopolská 135, 612 65, Brno, Czech Republic.

Guanine quadruplexes (G4s) are noncanonical forms of nucleic acids that are frequently found in genomes. The stability of G4s depends, among other factors, on the number of G-tetrads. Three- or four-tetrad G4s and antiparallel two-tetrad G4s have been characterized experimentally; however, the existence of an intramolecular (i. Read More

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The structures of E. coli NfsA bound to the antibiotic nitrofurantoin; to 1,4-benzoquinone and to FMN.

Biochem J 2021 Jul;478(13):2601-2617

School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, U.K.

NfsA is a dimeric flavoprotein that catalyses the reduction in nitroaromatics and quinones by NADPH. This reduction is required for the activity of nitrofuran antibiotics. The crystal structure of free Escherichia coli NfsA and several homologues have been determined previously, but there is no structure of the enzyme with ligands. Read More

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Development of IL-15/IL-15Rα sushi domain-IgG4 Fc complexes in Pichia pastoris with potent activities and prolonged half-lives.

Microb Cell Fact 2021 Jun 9;20(1):115. Epub 2021 Jun 9.

Department of Oncology of the First Affiliated Hospital, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230027, Anhui, China.

Background: Interleukin-15 (IL-15) is a critical cytokine for the development, proliferation, and function of natural killer (NK) cells, NKT cells, and CD8 memory T cells and has become one of the most promising protein molecules for the treatment of cancer and viral diseases. However, there are several limitations in applying IL-15 in therapy, such as its low yield in vitro, limited potency, and short half-life in vivo. To date, there are several recombinant IL-15 agonists based on configurational modifications that are being pursued in the treatment of cancer, such as ALT-803, which are mainly produced from mammalian cells. Read More

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Ready access to anhydrous anionic lanthanide acetates using imidazolium acetate ionic liquids as the reaction medium.

Chemistry 2021 Jun 7. Epub 2021 Jun 7.

The University of Alabama, College of Arts and Sciences, UNITED STATES.

The access to lanthanide acetate coordination compounds is challenged by the tendency of lanthanides to coordinate water and the plethora of acetate coordination modes. We developed a straightforward, reproducible synthetic procedure by reaction of lanthanide chloride hydrates with defined ratios of the ionic liquid (IL) 1-ethyl-3-methylimidazolium acetate ([C 2 mim][OAc]). This reaction pathway leads to two isostructural crystalline anhydrous coordination complexes, the polymeric [C 2 mim] n [{Ln 2 (OAc) 7 } n ] and the dimeric [C 2 mim] 2 [Ln 2 (OAc) 8 ], based on the ion size and the ratio of IL used. Read More

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Aryl urea substituted fatty acids: a new class of protonophoric mitochondrial uncoupler that utilises a synthetic anion transporter.

Chem Sci 2020 Aug 19;11(47):12677-12685. Epub 2020 Aug 19.

Discipline of Pharmacology, School of Medical Sciences, University of Sydney Sydney NSW 2006 Australia.

Respiring mitochondria establish a proton gradient across the mitochondrial inner membrane (MIM) that is used to generate ATP. Protein-independent mitochondrial uncouplers collapse the proton gradient and disrupt ATP production by shuttling protons back across the MIM in a protonophoric cycle. Continued cycling relies on the formation of MIM-permeable anionic species that can return to the intermembrane space after deprotonation in the mitochondrial matrix. Read More

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Chemical constituents from coconut waste and their evaluation as potential antiviral agents against SARS-CoV-2.

S Afr J Bot 2021 Sep 28;141:278-289. Epub 2021 May 28.

Department of Pharmacognosy, Faculty of Pharmacy, Kafrelsheikh University, 33516, Egypt.

Eleven compounds were isolated from the ethyl acetate extract of L endocarp, jezonofol , scirpusin A , cassigarol G , maackin A , threoguiacyl glycerol-8'-vanillic acid ether , erythroguiacyl glycerol-8'-vanillic acid ether , apigenin-7---D-glucoside , piceatannol , -hydroxy-benzoic acid , protocatechuic acid and vanillic acid . Compounds - were isolated for the first time from the plant. The isolated compounds were virtually screened against four critical components of severe acute respiratory syndrome corona virus 2 (SARS-CoV-2), the main protease (M), papain-like protease (PL), nonstructural protein 13 (nsp13) and RNA dependent RNA polymerase (RdRp). Read More

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September 2021

The structure-function relationship of a signaling-competent, dimeric Reelin fragment.

Structure 2021 Jun 1. Epub 2021 Jun 1.

Child Health Institute of New Jersey, New Brunswick, NJ 08901, USA; Department of Neuroscience and Cell Biology, Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, New Brunswick, NJ 08901, USA; School of Biological Sciences, Victoria University of Wellington, Wellington 6012, New Zealand. Electronic address:

Reelin operates through canonical and non-canonical pathways that mediate several aspects of brain development and function. Reelin's dimeric central fragment (CF), generated through proteolytic cleavage, is required for the lipoprotein-receptor-dependent canonical pathway activation. Here, we analyze the signaling properties of a variety of Reelin fragments and measure the differential binding affinities of monomeric and dimeric CF fragments to lipoprotein receptors to investigate the mode of canonical signal activation. Read More

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Total Synthesis of (±)-Jujuyane.

Org Lett 2021 Jun 3;23(12):4651-4656. Epub 2021 Jun 3.

Department of Chemistry, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Republic of Korea.

The first total synthesis of (±)-jujuyane, a cyclooctanoid natural product, was accomplished from a (5 + 3) dimerization product of oxidopyrylium ylide that forms the cyclooctanoid core structure along with inherited stereochemical bias. Selective functional group modifications of the highly oxygenated dimeric structure, followed by the tactical functional group manipulation around the eight-membered carbocyclic core, enabled the total synthesis of (±)-jujuyane, which will serve a guide for future applications of oxidopyrylium dimers to the natural product total synthesis. Read More

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Expression and analysis of the SAM-dependent RNA methyltransferase Rsm22 from Saccharomyces cerevisiae.

Acta Crystallogr D Struct Biol 2021 Jun 19;77(Pt 6):840-853. Epub 2021 May 19.

Faculty of Biochemistry and Molecular Medicine, University of Oulu, Aapistie 7B, FIN-90220 Oulu, Finland.

The Saccharomyces cerevisiae Rsm22 protein (Sc-Rsm22), encoded by the nuclear RSM22 (systematic name YKL155c) gene, is a distant homologue of Rsm22 from Trypanosoma brucei (Tb-Rsm22) and METTL17 from mouse (Mm-METTL17). All three proteins have been shown to be associated with mitochondrial gene expression, and Sc-Rsm22 has been documented to be essential for mitochondrial respiration. The Sc-Rsm22 protein comprises a polypeptide of molecular weight 72. Read More

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"Soft" oxidative coupling of methane to ethylene: Mechanistic insights from combined experiment and theory.

Proc Natl Acad Sci U S A 2021 Jun;118(23)

Department of Chemistry, Northwestern University, Evanston, IL 60208;

The oxidative coupling of methane to ethylene using gaseous disulfur (2CH + S → CH + 2HS) as an oxidant (SOCM) proceeds with promising selectivity. Here, we report detailed experimental and theoretical studies that examine the mechanism for the conversion of CH to CH over an FeO-derived FeS catalyst achieving a promising ethylene selectivity of 33%. We compare and contrast these results with those for the highly exothermic oxidative coupling of methane (OCM) using O (2CH + O → CH + 2HO). Read More

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Enzymatic characterization of a novel recombinant 1,3-α-3,6-anhydro-L-galactosidase specific for neoagarobiose hydrolysis into monosaccharides.

Appl Microbiol Biotechnol 2021 Jun 31;105(11):4621-4634. Epub 2021 May 31.

Laboratory of Immunobiology, School of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University, Daegu, 41566, Republic of Korea.

Two GH117 family α-neoagarobiose hydrolases (GH117A α-NABH and GH117B α-NABH) from the freshwater agar-degrading Cellvibrio sp. KY-GH-1 were expressed and purified as recombinant His-tagged proteins using an Escherichia coli expression system to compare activities. The amino acid sequence of GH117A α-NABH (364 amino acids, 40. Read More

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Bioinspired Brønsted Acid-Promoted Regioselective Tryptophan Isoprenylations.

ACS Omega 2021 Apr 12;6(16):10840-10858. Epub 2021 Apr 12.

Departments of Chemistry & Biology, Indian Institute of Science Education and Research, Tirupati 517507, Andhra Pradesh India.

Tryptophan-containing isoprenoid indole alkaloid natural products are well known for their intricate structural architectures and significant biological activities. Nature employs dimethylallyl tryptophan synthases (DMATSs) or aromatic indole prenyltransferases (iPTs) to catalyze regio- and stereoselective prenylation of l-Trp. Regioselective synthetic routes that isoprenylate -Trp-Trp in a 2,5-diketopiperazine (DKP) core, in a desymmetrizing manner, are nonexistent and are highly desirable. Read More

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A general approach on the surfactants use and their properties in drug delivery systems.

Curr Pharm Des 2021 May 25. Epub 2021 May 25.

Graduate Program in Pharmaceutical Sciences, State University of Paraíba, Campina Grnde, Brazil.

Surfactants are amphiphilic molecules of great interest in the pharmaceutical field due to their use in combination with other adjuvants to solubilize poor soluble drugs, improve their dissolution profile, promote permeation, increase drug delivery systems stabilization, among other characteristics. Literature shows that surfactants are included in several pharmaceutical forms composition: tablets, solid dispersions, emulsions, microemulsions, nanoemulsions, liposomes, and niosomes. This review aims to elucidate the different classes of surfactants based on their charges (cationic, anionic, nonionic, zwitterionic, and dimeric), the micelles formation process, and how surfactants molecules geometry can affect this phenomenon. Read More

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A chameleonic macrocyclic peptide with drug delivery applications.

Chem Sci 2021 Apr 11;12(19):6670-6683. Epub 2021 Apr 11.

The University of Queensland, School of Biomedical Sciences Brisbane QLD 4072 Australia

Head-to-tail cyclized peptides are intriguing natural products with unusual properties. The PawS-Derived Peptides (PDPs) are ribosomally synthesized as part of precursors for seed storage albumins in species of the daisy family, and are post-translationally excised and cyclized during proteolytic processing. Here we report a PDP twice the typical size and with two disulfide bonds, identified from seeds of . Read More

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