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Synthetic biology

Grace Yim, Wenliang Wang, Maulik N Thaker, Stephanie Tan, Gerard D Wright
Modification of natural product backbones is a proven strategy for the development of clinically useful antibiotics. Such modifications have traditionally been achieved through medicinal chemistry strategies or via in vitro enzymatic activities. In an orthogonal approach, engineering of biosynthetic pathways using synthetic biology techniques can generate chemical diversity. Here we report the use of a minimal teicoplanin class glycopeptide antibiotic (GPA) scaffold expressed in a production-optimized Streptomyces coelicolor strain to expand GPA chemical diversity...
September 9, 2016: ACS Infectious Diseases
James N Ayres, Kenneth B Ling, Louis C Morrill
A one-pot N-cyanation of secondary amines has been developed using trichloroacetonitrile as an inexpensive cyano source. A diverse range of cyclic and acyclic secondary amines can be readily transformed into the corresponding cyanamides in good isolated yields, with the method successfully utilized in the final synthetic step of a biologically active rolipram-derived cyanamide. This approach exhibits distinct selectivity when compared to the use of highly toxic cyanogen bromide.
October 18, 2016: Organic Letters
Oleksandr Zagorodko, Juan José Arroyo-Crespo, Vicent J Nebot, María J Vicent
Synthetic polypeptides or polyamino acids have become a useful and multifunctional platform in advanced drug delivery studies. Nonetheless, the full potential of these systems has yet to be achieved. The final structure of polypeptide conjugates and their in vivo behavior are dependent on an extraordinarily complex pattern of interconnected physico-chemical and structural parameters, making sophisticated directional design of such systems difficult and often unachievable. In this review, the authors aim to discuss the role of these parameters in the successful design of different drug delivery architectures and to delineate some basic correlations between structure, properties, and the biological behavior of polypeptide-based conjugates...
October 18, 2016: Macromolecular Bioscience
Martina F Callaghan, Siawoosh Mohammadi, Nikolaus Weiskopf
Quantitative MRI (qMRI) provides standardized measures of specific physical parameters that are sensitive to the underlying tissue microstructure and are a first step towards achieving maps of biologically relevant metrics through in vivo histology using MRI. Recently proposed models have described the interdependence of qMRI parameters. Combining such models with the concept of image synthesis points towards a novel approach to synthetic qMRI, in which maps of fundamentally different physical properties are constructed through the use of biophysical models...
October 18, 2016: NMR in Biomedicine
Christine E Mona, Élie Besserer-Offroy, Jérôme Cabana, Richard Leduc, Pierre Lavigne, Nikolaus Heveker, Éric Marsault, Emanuel Escher
A combination of the CXCR4 inverse agonist T140 with N-terminal CXCL12 oligopeptides has produced the first nanomolar synthetic CXCR4 agonists. In these agonists, the inverse agonistic portion provides affinity whereas the N-terminal CXCL12 sequence induces receptor activation. Several CXCR4 crystal structures exist with either CVX15, an inverse agonist closely related to T140 and IT1t, a small molecule; we therefore attempted to produce another CXCL12 oligopeptide combination with IT1t. For this purpose, a primary amino group was introduced by total synthesis into one of the methyl groups of IT1t, serving as an anchoring point for the oligopeptide graft...
October 18, 2016: Organic & Biomolecular Chemistry
Zhigang Wu, Yunpeng Liu, Cheng Ma, Lei Li, Jing Bai, Lauren Byrd-Leotis, Yi Lasanajak, Yuxi Guo, Liuqing Wen, He Zhu, Jing Song, Yanhong Li, David A Steinhauer, David F Smith, Baohua Zhao, Xi Chen, Wanyi Guan, Peng George Wang
Glycans play diverse roles in a wide range of biological processes. Research on glycan-binding events is essential for learning their biological and pathological functions. However, the functions of terminal and internal glycan epitopes exhibited during binding with glycan-binding proteins (GBPs) and/or viruses need to be further identified. Therefore, a focused library of 36 biantennary asparagine (Asn)-linked glycans with some presenting tandem glycan epitopes was synthesized via a combined Core Isolation/Enzymatic Extension (CIEE) and one-pot multienzyme (OPME) synthetic strategy...
October 18, 2016: Organic & Biomolecular Chemistry
Guoyun Zhang, Aiguo Duan, Jianguo Zhang, Caiyun He
Long non-coding RNAs (lncRNAs), which are >200nt longer transcripts, potentially play important roles in almost all biological processes in plants and mammals. However, the functions and profiles of lncRNAs in fruit is less understood. Therefore, it is urgent and necessary to identify and analyze the functions of lncRNAs in sea buckthorns. Using RNA-sequencing, we synthetically identified lncRNAs in mature fruit from the red and yellow sea buckthorn. We obtained 567,778,938 clean reads from six samples and identified 3428 lncRNAs in mature fruit, including 2498 intergenic lncRNAs, 593 anti-sense lncRNAs, and 337 intronic lncRNAs...
October 14, 2016: Gene
Christian Brinch Mollerup, Petur Weihe Dalsgaard, Marie Mardal, Kristian Linnet
High-resolution mass spectrometry (HRMS) is widely used for the drug screening of biological samples in clinical and forensic laboratories. With the continuous addition of new psychoactive substances (NPS), keeping such methods updated is challenging. HRMS allows for combined targeted and non-targeted screening; first, peaks are identified by software algorithms, and identifications are based on reference standard data. Remaining unknown peaks are attempted identified with in silico and literature data. However, several thousand peaks remain where most are unidentifiable or uninteresting in drug screening...
October 17, 2016: Drug Testing and Analysis
Julie A Birt, YingMeei Tan, Neelufar Mozaffarian
OBJECTIVES: To better understand the real-world characteristics and costs of Sjögren's syndrome (SS). METHODS: Analysing the MarketScan Commercial Claims database from Jan. 1, 2006 to Dec. 31, 2011, we identified 10,414 patients ≥18 years old newly diagnosed with SS. Patient characteristics, drugs (commonly used for SS), resource utilisation, and medical costs were evaluated for 12 months pre- and post-diagnosis. RESULTS: Mean age was 55 years; 90% were female...
October 7, 2016: Clinical and Experimental Rheumatology
Xiang Sun, Hongwei Zhang, Longhua Luo, Kezhao Zhong, Yushui Ma, Linlin Fan, Da Fu, Lijuan Wan
The identification of markers for disease diagnostic, prognostic, or predictive purposes will have a great effect in improving patient management. Proteomic‑based approaches for biomarker discovery are promising strategies used in cancer research. In this study, we performed quantitative proteomic analysis on four patients including clear cell renal cell carcinoma (ccRCC) and paired adjacent non‑cancerous renal tissues using label‑free quantitative proteomics and liquid chromatography‑tandem mass spectrometry (LC‑MS/MS) to identify differentially expressed proteins...
October 11, 2016: Oncology Reports
Arvind Sivasubramanian, Patricia Estep, Heather Lynaugh, Yao Yu, Adam Miles, Josh Eckman, Kevin Schutz, Crystal Piffath, Nadthakarn Boland, Rebecca Hurley Niles, Stéphanie Durand, Todd Boland, Maximiliano Vásquez, Yingda Xu, Yasmina Abdiche
Successful discovery of therapeutic antibodies hinges on the identification of appropriate affinity binders targeting a diversity of molecular epitopes presented by the antigen. Antibody campaigns that yield such broad "epitope coverage" increase the likelihood of identifying candidates with the desired biological functions. Accordingly, epitope binning assays are employed in the early discovery stages to partition antibodies into epitope families or "bins" and prioritize leads for further characterization and optimization...
October 17, 2016: MAbs
Nathan Crook, Joseph Abatemarco, Jie Sun, James M Wagner, Alexander Schmitz, Hal S Alper
Directed evolution remains a powerful, highly generalizable approach for improving the performance of biological systems. However, implementations in eukaryotes rely either on in vitro diversity generation or limited mutational capacities. Here we synthetically optimize the retrotransposon Ty1 to enable in vivo generation of mutant libraries up to 1.6 × 10(7) l(-1) per round, which is the highest of any in vivo mutational generation approach in yeast. We demonstrate this approach by using in vivo-generated libraries to evolve single enzymes, global transcriptional regulators and multi-gene pathways...
October 17, 2016: Nature Communications
Giorgia Macedonio, Azzurra Stefanucci, Cristina Maccallini, Sako Mirzaie, Ettore Novellino, Adriano Mollica
The endocannabinoid system is activated by the binding of natural arachidonic acid derivatives (endogenous cannabinoids or endocannabinoids) as lipophilic messengers to cannabinoid receptors CB1 and CB2. The endocannabinoid system comprises also many hydrolytic enzymes responsible for the endocannabinoids cleavage, such as FAAH and MAGL. These two enzymes are possible therapeutic targets for the development of new drugs as indirect cannabinoid agonists. Recently a new family of endocannabinoid modulators was discovered; the lead of this family is the nonapeptide hemopressin produced from enzymatic cleavage of the α-chain of hemoglobin and acting as negative allosteric modulator of CB1...
October 7, 2016: Protein and Peptide Letters
Sergio Iannazzo, Gianluca Furneri, Federica Demma, Chiara Distante, Simone Parisi, Veronica Berti, Enrico Fusaro
INTRODUCTION: Chronic inflammatory rheumatic diseases (RDs) trigger high costs for healthcare systems and society due to the disability and comorbidity associated with these disease entities. The aim of this study was to analyze patients with RD, assess the use of conventional synthetic and biologic therapies, and estimate the overall cost of treatment in Italy. METHODS: Administrative healthcare claims from the Piedmont region in Northwest Italy were reviewed to identify patients who received disease-modifying antirheumatic drugs (DMARDs) between 2007 and 2010...
June 2016: Rheumatol Ther
Andrew Kd Younger, Neil Chandra Dalvie, Austin G Rottinghaus, Joshua N Leonard
Efforts to engineer microbial factories have benefitted from mining biological diversity and high throughput synthesis of novel enzymatic ensembles, yet screening and optimizing metabolic pathways remain rate-limiting steps. Metabolite-responsive biosensors may help to address these persistent challenges by enabling the monitoring of metabolite levels in individual cells and metabolite-responsive feedback control. We are currently limited to naturally-evolved biosensors, which are insufficient for monitoring many metabolites of interest...
October 17, 2016: ACS Synthetic Biology
Joshua Fern, Dominic Scalise, Angelo Cangialosi, Dylan Howie, Leo Potters, Rebecca Schulman
Chemical circuits can coordinate elaborate sequences of events in cells and tissues, from the self-assembly of biological complexes to the sequence of embryonic development. However, autonomously directing the timing of events in synthetic systems using chemical signals remains challenging. Here we demonstrate that a simple synthetic DNA strand-displacement circuit can release target sequences of DNA into solution at a constant rate after a tunable delay that can range from hours to days. The rates of DNA release can be tuned to the order of 1-100 nM per day...
October 17, 2016: ACS Synthetic Biology
Lei Zhou, Jing Liu, Faqin Dong
Mackinawite (FeS), widespread in low temperature aquatic environments, is generally considered to be the first Fe sulfide formed in sedimentary environments which has shown effective immobilization of heavy metals and toxic oxyanions through various sorption reactions. The spectroscopic study researches on mackinawite formed by FRB and SRB and its environmental implication for in-situ remediation of acid mine drainage where contains large amounts of Fe(3+) and SO4(2-). The XRD result of biologically synthetic particles shows that these particles are mainly composed of mackinawite (FeS0...
September 29, 2016: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
Jessica G Perez, Jessica C Stark, Michael C Jewett
Cell-free protein synthesis (CFPS) technologies have enabled inexpensive and rapid recombinant protein expression. Numerous highly active CFPS platforms are now available and have recently been used for synthetic biology applications. In this review, we focus on the ability of CFPS to expand our understanding of biological systems and its applications in the synthetic biology field. First, we outline a variety of CFPS platforms that provide alternative and complementary methods for expressing proteins from different organisms, compared with in vivo approaches...
October 14, 2016: Cold Spring Harbor Perspectives in Biology
Guillem Rigaill, Sandrine Balzergue, Véronique Brunaud, Eddy Blondet, Andrea Rau, Odile Rogier, José Caius, Cathy Maugis-Rabusseau, Ludivine Soubigou-Taconnat, Sébastien Aubourg, Claire Lurin, Marie-Laure Martin-Magniette, Etienne Delannoy
Numerous statistical pipelines are now available for the differential analysis of gene expression measured with RNA-sequencing technology. Most of them are based on similar statistical frameworks after normalization, differing primarily in the choice of data distribution, mean and variance estimation strategy and data filtering. We propose an evaluation of the impact of these choices when few biological replicates are available through the use of synthetic data sets. This framework is based on real data sets and allows the exploration of various scenarios differing in the proportion of non-differentially expressed genes...
October 14, 2016: Briefings in Bioinformatics
Mirko Nowak, Uwe Freudenberg, Mikhail V Tsurkan, Carsten Werner, Kandice R Levental
Matrix systems used to study complex three-dimensional (3D) cellular processes like mammary epithelial tissue morphogenesis and tumorigenesis ex vivo often require ill-defined biological components, which lead to poor reproducibility and a lack of control over physical parameters. In this study, a well-defined, tunable synthetic biohybrid hydrogel composed of the glycosaminoglycan heparin, star-shaped poly(ethylene glycol) (starPEG), and matrix metalloproteinase- (MMP-) cleavable crosslinkers was applied to dissect the biophysical and biochemical signals promoting human mammary epithelial cell (MEC) morphogenesis...
October 6, 2016: Biomaterials
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