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Synthetic biology

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https://www.readbyqxmd.com/read/28644392/development-of-bone-targeting-drugs
#1
REVIEW
Molly Stapleton, Kazuki Sawamoto, Carlos J Alméciga-Díaz, William G Mackenzie, Robert W Mason, Tadao Orii, Shunji Tomatsu
The skeletal system, comprising bones, ligaments, cartilage and their connective tissues, is critical for the structure and support of the body. Diseases that affect the skeletal system can be difficult to treat, mainly because of the avascular cartilage region. Targeting drugs to the site of action can not only increase efficacy but also reduce toxicity. Bone-targeting drugs are designed with either of two general targeting moieties, aimed at the entire skeletal system or a specific cell type. Most bone-targeting drugs utilize an affinity to hydroxyapatite, a major component of the bone matrix that includes a high concentration of positively-charged Ca(2+)...
June 23, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28644007/cyclotides-as-tools-in-chemical-biology
#2
Simon J de Veer, Joachim Weidmann, David J Craik
Among the various molecules that plants produce for defense against pests and pathogens, cyclotides stand out as exceptionally stable and structurally unique. These ribosomally synthesized peptides are around 30 amino acids in size, and are stabilized by a head-to-tail cyclic peptide backbone and three disulfide bonds that form a cystine knot. They occur in certain plants of the Rubiaceae, Violaceae, Cucurbitaceae, Fabaceae, and Solanaceae families, with an individual plant producing up to hundreds of different cyclotides...
June 23, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28642488/biomimetic-molecular-signaling-using-dna-walkers-on-microparticles
#3
Tulsi Ram Damase, Adam Spencer, Bamidele Samuel, Peter B Allen
We report the release of catalytic DNA walkers from hydrogel microparticles and the detection of those walkers by substrate-coated microparticles. This might be considered a synthetic biology analog of molecular signal release and reception. One type of particles was coated with components of a DNA one-step strand displacement (OSD) reaction to release the walker. A second type of particle was coated with substrate (or "track") for the molecular walker. We distinguish these particle types using fluorescence barcoding: we synthesized and distinguished multiple particle types with multicolor fluorescence microscopy and automated image analysis software...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28642435/a-catalytic-fluoride-rebound-mechanism-for-c-sp-3-cf3-bond-formation
#4
Mark D Levin, Tiffany Q Chen, Megan E Neubig, Cynthia M Hong, Cyril A Theulier, Ilia J Kobylianskii, Mustafa Janabi, James P O'Neil, F Dean Toste
The biological properties of trifluoromethyl compounds have led to their ubiquity in pharmaceuticals, yet their chemical properties have made their preparation a substantial challenge, necessitating innovative chemical solutions. We report the serendipitous discovery of a borane-catalyzed formal C(sp(3))-CF3 reductive elimination from Au(III) that accesses these compounds by a distinct mechanism proceeding via fluoride abstraction, migratory insertion, and C-F reductive elimination to achieve a net C-C bond construction...
June 23, 2017: Science
https://www.readbyqxmd.com/read/28642234/reconfiguration-of-dna-molecular-arrays-driven-by-information-relay
#5
Jie Song, Zhe Li, Pengfei Wang, Travis Meyer, Chengde Mao, Yonggang Ke
Information relay at the molecular level is an essential phenomenon in numerous chemical and biological processes, such as intricate signaling cascades. One key challenge in synthetic molecular self-assembly is to construct artificial structures that imitate these complex behaviors in controllable systems. We demonstrated prescribed, long-range information relay in an artificial molecular array assembled from modular DNA structural units. The dynamic DNA molecular array exhibits transformations with programmable initiation, propagation, and regulation...
June 22, 2017: Science
https://www.readbyqxmd.com/read/28642195/how-lipid-droplets-tag-along-glycerolipid-synthetic-enzymes-and-lipid-storage
#6
REVIEW
Huan Wang, Michael V Airola, Karen Reue
Triacylglycerols (TAG) serve as the predominant form of energy storage in mammalian cells, and TAG synthesis influences conditions such as obesity, fatty liver, and insulin resistance. In most tissues, the glycerol 3-phosphate pathway enzymes are responsible for TAG synthesis, and the regulation and function of these enzymes is therefore important for metabolic homeostasis. Here we review the sites and regulation of glycerol-3-phosphate acyltransferase (GPAT), acylglycerol-3-phosphate acyltransferase (AGPAT), lipin/phosphatidic acid phosphatase (PAP), and diacylglycerol acyltransferase (DGAT) enzyme action...
June 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28642126/molecular-and-hydrodynamic-properties-of-human-epidermal-growth-factor-receptor-her2-extracellular-domain-and-its-homodimer-experiments-and-multi-scale-simulations
#7
J F Vega, J Ramos, V Cruz, E Vicente-Alique, E Sánchez-Sánchez, A Sánchez-Fernández, Y Wang, P Hu, J Cortés, J Martínez-Salazar
BACKGROUND: In a broad range of human carcinomas gene amplification leads to HER2 overexpression, which has been proposed to cause spontaneous dimerization and activation in the absence of ligand. This makes HER2 attractive as a therapeutic target. However, the HER2 homodimerization mechanism remains unexplored. It has been suggested that the "back-to-back" homodimer does not form in solution. Notwithstanding, very recently the crystal structure of the HER2 extracellular domain homodimer formed with a "back-to-head" interaction has been resolved...
June 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28641558/bis-2-aminoimidazolines-and-bisguanidines-synthetic-approaches-antiparasitic-activity-and-dna-binding-properties
#8
Christophe Dardonville, J Jonathan Nué Martínez
BACKGROUND: Parasitic diseases caused by protozoan parasites of the genus Trypanosoma and Plasmodium cause some of the deadliest and disabling human infections in tropical and subtropical areas. Diphenyl-based bis(2-phenylimino)imidazolidines and bisguanidines are extremely potent antiparasitic agents against Trypanosoma brucei (etiological agent of African trypanosomiasis) and Plasmodium falciparum (etiological agent of severe malaria). Many of these compounds are also curative in mouse models of stage 1 African trypanosomiasis representing promising leads for the development of antitrypanosomal drugs...
June 22, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28641526/biology-oriented-synthesis-bios-of-piperine-derivatives-and-their-comparative-analgesic-and-antiinflammatory-activities
#9
Ammar Yasir, Saiqa Ishtiaq, Muhammad Jahangir, Muhammad Ajaib, Uzma Salar, Khalid Mohammed Khan
BACKGROUND: Serious side effects such as gastric intestinal ulcer, bleeding etc. are associated with most of the antiinflammatory and analgesic drugs. So there is a need to search novel, potent, and safer antiinflammatory and analgesic drug. METHOD: Based on "biology-oriented synthesis approach", piperine alkaloid was isolated from Piper nigrum L. and some derivatives of piperine having azomethine, sulfamoyl, propanoyl, acetamoyl and heterocyclic oxadiazole were synthesized...
June 22, 2017: Medicinal Chemistry
https://www.readbyqxmd.com/read/28641051/beneficial-role-of-citrus-fruit-polyphenols-against-hepatic-dysfunctions-a-review
#10
Md Mohabbulla Mohib, Kazi Afnan, Tasfiq Zaman Paran, Salma Khan, Juthika Sarker, Nahid Hasan, Istiaque Hasan, Md Abu Taher Sagor
Alcoholic liver diseases and virus-induced hepatic dysfunctions are prevalent in western countries. Evidence also suggests that hyperglycemia and insulin resistance are key players in the development of hepatic diseases and their complications. Since the comorbid diseases like obesity, diabetes and vascular dysfunctions primarily affect liver, the modern therapies against other hepatic dysfunctions are becoming a major challenge to treat. In addition to these, polypharmacy and adverse drug reactions (ADRs) are further aggravating the phenomenon...
June 22, 2017: Journal of Dietary Supplements
https://www.readbyqxmd.com/read/28641003/synthesis-and-anti-inflammatory-evaluation-of-2-aminobenzaldehydes-via-ir-iii-catalyzed-c-h-amidation-of-aldimines-with-acyl-azides
#11
Saegun Kim, Prashant Chakrasali, Hyo Sun Suh, Neeraj Kumar Mishra, Taeyoung Kim, Sang Hoon Han, Hyung Sik Kim, Byung-Moo Lee, Soo Bong Han, In Su Kim
The aldimine-directed C-H amidation of various arenes with N-acyl azides as amidation surrogates under cationic iridium(III) catalysis is described. This transformation efficiently provides a range of 2-aminobenzaldehydes derivatives with excellent site-selectivity and functional group compatibility. The resulting 2-aminobenzaldehyde framework provides facile access to a range of biologically interesting heterocycles. In addition, all synthetic compounds were screened for anti-inflammatory activity against interleukin-1β (IL-1β) and tumor necrosis factor alpha (TNF-α) with lipopolysaccharide (LPS)-induced RAW264...
June 22, 2017: Journal of Organic Chemistry
https://www.readbyqxmd.com/read/28640622/catalytic-asymmetric-synthesis-of-butenolides-and-butyrolactones
#12
Bin Mao, Martín Fañanás-Mastral, Ben L Feringa
γ-Butenolides, γ-butyrolactones, and derivatives, especially in enantiomerically pure form, constitute the structural core of numerous natural products which display an impressive range of biological activities which are important for the development of novel physiological and therapeutic agents. Furthermore, optically active γ-butenolides and γ-butyrolactones serve also as a prominent class of chiral building blocks for the synthesis of diverse biological active compounds and complex molecules. Taking into account the varying biological activity profiles and wide-ranging structural diversity of the optically active γ-butenolide or γ-butyrolactone structure, the development of asymmetric synthetic strategies for assembling such challenging scaffolds has attracted major attention from synthetic chemists in the past decade...
June 22, 2017: Chemical Reviews
https://www.readbyqxmd.com/read/28640544/interactions-of-neurons-with-physical-environments
#13
REVIEW
Michal Marcus, Koby Baranes, Matthew Park, Insung S Choi, Kyungtae Kang, Orit Shefi
Nerve growth strongly relies on multiple chemical and physical signals throughout development and regeneration. Currently, a cure for injured neuronal tissue is an unmet need. Recent advances in fabrication technologies and materials led to the development of synthetic interfaces for neurons. Such engineered platforms that come in 2D and 3D forms can mimic the native extracellular environment and create a deeper understanding of neuronal growth mechanisms, and ultimately advance the development of potential therapies for neuronal regeneration...
June 22, 2017: Advanced Healthcare Materials
https://www.readbyqxmd.com/read/28638777/heterobifunctional-dyes-highly-fluorescent-linkers-based-on-cyanine-dyes
#14
Virginia Wycisk, Katharina Achazi, Ole Hirsch, Christian Kuehne, Jens Dernedde, Rainer Haag, Kai Licha
Herein, we present a new synthetic route to cyanine-based heterobifunctional dyes and their application as fluorescent linkers between polymers and biomolecules. The synthesized compounds, designed in the visible spectral range, are equipped with two different reactive groups for highly selective conjugation under physiological conditions. By applying indolenine precursors with functionalized benzenes, we achieved water-soluble asymmetric cyanine dyes bearing maleimido and N-hydroxysuccinimidyl functionalities in a three-step synthesis...
June 2017: ChemistryOpen
https://www.readbyqxmd.com/read/28638082/tandem-malonate-based-glucosides-tmgs-for-membrane-protein-structural-studies
#15
Hazrat Hussain, Jonas S Mortensen, Yang Du, Claudia Santillan, Orquidea Ribeiro, Juyeon Go, Parameswaran Hariharan, Claus J Loland, Lan Guan, Brian K Kobilka, Bernadette Byrne, Pil Seok Chae
High-resolution membrane protein structures are essential for understanding the molecular basis of diverse biological events and important in drug development. Detergents are usually used to extract these bio-macromolecules from the membranes and maintain them in a soluble and stable state in aqueous solutions for downstream characterization. However, many eukaryotic membrane proteins solubilized in conventional detergents tend to undergo structural degradation, necessitating the development of new amphiphilic agents with enhanced properties...
June 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28637559/complex-abdominal-wall-hernia-repair-in-contaminated-surgical-fields-factors-affecting-the-choice-of-prosthesis
#16
Manuel López-Cano, María Teresa Quiles, José Antonio Pereira, Manuel Armengol-Carrasco, María Antonia Arbós Vía
To compare patients with complex abdominal wall hernias undergoing surgical repair using synthetic nonabsorbable or biologic meshes in contaminated fields. Retrospective review of 62 patients with complex abdominal wall hernia with surgical repair in an elective setting and in the context of a clean-contaminated or contaminated fields (January 2009-April 2015). Two groups according to the prosthesis (synthetic nonabsorbable, n = 48 or biologic, n = 14). Mean follow-up was 24.6 (15.8) months. Clean-contaminated wounds were significantly more frequent in the synthetic group...
June 1, 2017: American Surgeon
https://www.readbyqxmd.com/read/28637397/ursolic-acid-derivatives-for-pharmaceutical-use-a-patent-review-2012-2016
#17
Hidayat Hussain, Ivan R Green, Iftikhar Ali, Ikhlas A Khan, Zulfiqar Ali, Abdullah M Al-Sadi, Ishtiaq Ahmed
Ursolic acid (UA), belongs to a group of pentacyclic triterpenoids and is known to possess some very interesting biological properties. Protocols have been developed in order to synthesize bioactive UA analogs which have resulted in numerous ursolic acid analogs being synthesized during the period 2012-2016. Ursolic acid and its analogues can be employed to treat various cancers, inflammatory diseases, diabetes, Parkinson's disease, Alzheimer's disease, hepatitis B, hepatitis C and AIDS to mention but a few...
June 21, 2017: Expert Opinion on Therapeutic Patents
https://www.readbyqxmd.com/read/28637365/insight-into-the-c-f-bond-mechanism-of-molecular-analogs-for-antibacterial-drug-design
#18
Junna Liu, Biyu Lv, Huaqing Liu, Xin Li, Weiping Yin
The activities of biological molecules usually rely on both of intra-molecular and intermolecular interactions between their function groups. These interactions include interonic attraction theory, Van der Waal's forces and the function of geometry on the individual molecules, whether they are naturally or synthetic. The purpose of this study was to evaluate the antibacterial activity of C-F bond compound using combination of experiments verification and theoretical calculation. We target on the insect natural products from the maggots of Chrysomyis megacephala Fabricius...
June 21, 2017: Natural Product Research
https://www.readbyqxmd.com/read/28637316/incorporating-comparative-genomics-into-the-design-test-learn-cycle-of-microbial-strain-engineering
#19
Maria Sardi, Audrey P Gasch
Engineering microbes with new properties is an important goal in industrial engineering, to establish biological factories for production of biofuels, commodity chemicals, and pharmaceutics. But engineering microbes to produce new compounds with high yield remains a major challenge toward economically viable production. Incorporating several modern approaches, including synthetic and systems biology, metabolic modeling, and regulatory rewiring have proven to significantly advance industrial strain engineering...
June 16, 2017: FEMS Yeast Research
https://www.readbyqxmd.com/read/28636874/next-generation-matrix-metalloproteinase-inhibitors-novel-strategies-bring-new-prospects
#20
REVIEW
Maxim Levin, Yael Udi, Inna Solomonov, Irit Sagi
Enzymatic proteolysis of cell surface proteins and extracellular matrix (ECM) is critical for tissue homeostasis and cell signaling. These proteolytic activities are mediated predominantly by a family of proteases termed matrix metalloproteinases (MMPs). The growing evidence in recent years that ECM and non-ECM bioactive molecules (e.g., growth factors, cytokines, chemokines, on top of matrikines and matricryptins) have versatile functions redefines our view on the roles matrix remodeling enzymes play in many physiological and pathological processes, and underscores the notion that ECM proteolytic reaction mechanisms represent master switches in the regulation of critical biological processes and govern cell behavior...
June 18, 2017: Biochimica et Biophysica Acta
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