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(Synthetic biology)

Claudia Schmid-Dannert, Fernando López-Gallego
During the past decades, biocatalysis has made important contributions to chemical manufacturing by using both whole-cell and cell-free biotransformation reactions. More recently, multi-enzyme systems that can run step-wise reactions in one-pot with high selectivity are increasingly being developed. The use of multiple isolated enzymes to perform a series of reactions offers operational and process advantages over the use of living or resting cells, but such cell free processes need to be optimized to meet industrial productivity and titer requirements...
December 11, 2018: Current Opinion in Chemical Biology
Brandon Campbell, Taylor Hood, Nathaniel Shank
Peptide nucleic acids (PNA) are one of many synthetic mimics of DNA and RNA that have found applications as biological probes, as nano-scaffold components, and in diagnostics. In an effort to use PNA as constructs for cellular delivery we investigated the possibility of installing a biologically susceptible disulfide bond in the backbone of a PNA oligomer. Here we report the synthesis of a new abasic Fmoc monomer containing a disulfide bond that can be incorporated into a PNA oligomer (DS-PNA) using standard solid phase peptide synthesis...
December 1, 2018: Bioorganic Chemistry
Xiang Liu, Lingtong Zhou, Peng Heng, Jingcheng Xiao, Junping Lv, Qingmiao Zhang, Michael E Hickey, Qin Tu, Jinyi Wang
The development of hepatocyte cultures in vitro holds great significance in the study of bioartificial liver support systems. Electrospun fiber cultures have received widespread attention as an effective method to culture hepatocytes in vitro. Polylactic acid (PLA) -a synthetic polymer with high biocompatibility and biodegradability- is widely used to fabricate electrospun fibers in the biomedical field. However, the use of PLA is limited in cell cultures due to its brittleness, strong hydrophobicity, and lack of biologically active functional groups...
September 28, 2018: Colloids and Surfaces. B, Biointerfaces
Morten H H Nørholm
A major aim of synthetic biology is the design of robust living systems for real-world applications. In seemingly contrast, evolution changes the living, exploring new survival strategies in response to environmental challenges. How do we cope with this paradox? Can we control or even exploit the molecular mechanisms of evolution for biotechnological and biosustainable innovation and will the principles of engineering lead to fundamental insights in evolutionary biology? A merger of synthetic biology with experimental evolution is occurring and it will radically accelerate the development of these scientific disciplines...
December 12, 2018: Microbial Biotechnology
Bei Yang, Yaohui Xu, Andrew Maxwell, Wonryull Koh, Ping Gong, Chaoyang Zhang
BACKGROUND: Reconstruction of gene regulatory networks (GRNs), also known as reverse engineering of GRNs, aims to infer the potential regulation relationships between genes. With the development of biotechnology, such as gene chip microarray and RNA-sequencing, the high-throughput data generated provide us with more opportunities to infer the gene-gene interaction relationships using gene expression data and hence understand the underlying mechanism of biological processes. Gene regulatory networks are known to exhibit a multiplicity of interaction mechanisms which include functional and non-functional, and linear and non-linear relationships...
December 14, 2018: BMC Systems Biology
Giuseppe Jurman, Michele Filosi, Roberto Visintainer, Samantha Riccadonna, Cesare Furlanello
Reconstructing a gene regulatory network from one or more sets of omics measurements has been a major task of computational biology in the last 20 years. Despite an overwhelming number of algorithms proposed to solve the network inference problem either in the general scenario or in an ad-hoc tailored situation, assessing the stability of reconstruction is still an uncharted territory and exploratory studies mainly tackled theoretical aspects. We introduce here empirical stability, which is induced by variability of reconstruction as a function of data subsampling...
2019: Methods in Molecular Biology
Christopher A Penfold, Iulia Gherman, Anastasiya Sybirna, David L Wild
Gaussian process dynamical systems (GPDS) represent Bayesian nonparametric approaches to inference of nonlinear dynamical systems, and provide a principled framework for the learning of biological networks from multiple perturbed time series measurements of gene or protein expression. Such approaches are able to capture the full richness of complex ODE models, and can be scaled for inference in moderately large systems containing hundreds of genes. Related hierarchical approaches allow for inference from multiple datasets in which the underlying generative networks are assumed to have been rewired, either by context-dependent changes in network structure, evolutionary processes, or synthetic manipulation...
2019: Methods in Molecular Biology
Fisayo A Olotu, Geraldene Munsamy, Mahmoud E S Soliman
Over the years, numerous synthetic approaches have been utilized in drug design to improve the pharmacological properties of naturally derived compounds and most importantly, minimize toxic effects associated with their transition to drugs. The reduction of complex bioderived compounds to simpler bioactive fragments has been identified as a viable strategy to develop lead compounds with improved activities and minimal toxicities. Although this 'reductive' strategy has been widely exemplified, underlying biological events remain unresolved, hence the unanswered question remains how does the fragmentation of a natural compound improve its bioactivity and reduce toxicities? Herein, using a combinatorial approach, we initialize a computational "proof-of- concept" to expound the differential pharmacological and antagonistic activities of a natural compound, Anguinomycin D, and its synthetic fragment, SB640 towards Exportin Chromosome Region Maintenance 1 (CRM1)...
2018: Computational and Structural Biotechnology Journal
Norbert Latruffe, Dominique Vervandier-Fasseur
T rans -resveratrol, the most well-known polyphenolic stilbenoid, is found in grapes and accordingly in wine and it is considered to be beneficial for human health, especially towards the aging-linked cell alterations by providing numerous biological activities, such as anti-oxidant, antitumoral, antiviral, anti-inflammatory, neuroprotective, and platelet anti-aggregation properties. Although trans -resveratrol is a promising molecule, it cannot be considered as a drug, due to its weak bio-availability and fast metabolism...
December 11, 2018: Diseases (Basel)
Caroline Bray, Pratik Gurnani, Edward D H Mansfield, Raoul Peltier, Sebastien Perrier
Fibroblast growth factors (FGF) are involved in a wide range of biological processes such as cell proliferation and differentiation. In living organisms, the binding of FGF to its receptors are mediated through electrostatic interactions between FGF and naturally occurring heparin. Despite its prevalent use in medicine, heparin carries notable limitations, namely; its extraction from natural sources (expensive, low yield and extensive purification), viral contamination, and batch-to-batch heterogeneity. In this work a range of synthetic homopolymers and copolymers of sodium 2-acrylamido-2-methylpropane sulfonate (AMPS®) were evaluated as potential FGF stabilisers...
December 13, 2018: Biomacromolecules
Felix Polten, Marc Reboll, Christian Widera, Tibor Kempf, Kerstin Bethmann, Priyanka Gupta, John Miglietta, A Pekcec, Jochen Tillmanns, Johann Bauersachs, Evangelos Giannitsis, Andreas Pich, Kai C Wollert
Myeloid-derived growth factor (MYDGF in humans, Mydgf in mice) is a secreted protein with previously unknown biological functions. In a recent study, Mydgf was shown to mediate cardiac repair after acute myocardial infarction (MI) in mice. Lack of a sensitive assay to measure MYDGF in the circulation has hampered its further investigation. Here, we developed a liquid chromatography/multiple reaction monitoring-mass spectrometry MYDGF assay, employing SDS-PAGE-based protein fractionation to deplete high-abundant proteins and a stable isotope-labeled synthetic standard peptide for quantification...
December 13, 2018: Analytical Chemistry
Ravi S Loka, Eric T Sletten, Uri Barash, Israel Vlodavsky, Hien M Nguyen
Heparanase, the sole heparan sulfate polysaccharide degrading endoglycosidase enzyme, regulates multiple biological activities that enhance malignant tumor progression. High levels of heparanase are present in all types of cancers and have been correlated with increased tumor size, angiogenic activity, enhanced metastasis, and poor patient prognosis. Herein, we report a systematic investigation of the effects of multivalent inhibition of heparanase. In the study, the sulfation pattern of the pendant disaccharide moiety on synthetic glycopolymers was synthetically manipulated to achieve best inhibition of heparanase...
December 13, 2018: ACS Applied Materials & Interfaces
Khemchand Surana, Bharatkumar Chaudhary, Monika Diwaker, Satyasheel Sharma
The benzophenone scaffold represents a ubiquitous structure in medicinal chemistry because it is found in several naturally occurring molecules which exhibit a variety of biological activities, such as anticancer, anti-inflammatory, antimicrobial, and antiviral. In addition, various synthetic benzophenone motifs are present in marketed drugs. They also represent important ingredients in perfumes and can act as photoinitiators. This review will provide an overview of benzophenone moieties with medicinal aspects synthesized in the last 15 years and will cover the most potent molecule in each report...
November 1, 2018: MedChemComm
Yitian Xu, Lu Huang, Jonathan L Kirschman, Daryll A Vanover, Pooja M Tiwari, Philip J Santangelo, Xiling Shen, David G Russell
Therapeutic strategies based on in vitro-transcribed mRNA (IVT) are attractive because they avoid the permanent signature of genomic integration that is associated with DNA-based therapy and result in the transient production of proteins of interest. To date, IVT has mainly been used in vaccination protocols to generate immune responses to foreign Ags. In this "proof-of-principle" study, we explore a strategy of combinatorial IVT to recruit and reprogram immune effector cells to acquire divergent biological functions in mice in vivo...
December 12, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Na Ye, Bang Li, Qi Mao, Eric A Wold, Sheng Tian, John A Allen, Jia Zhou
While G protein-coupled receptors (GPCRs) are recognized as pivotal drug targets involved in multiple physiological and pathological processes, the majority of GPCRs including orphan GPCRs (oGPCRs) are unexploited. GPR88, a brain-specific oGPCR with particularly robust expression in the striatum, regulates diverse brain and behavioral functions including cognition, mood, movement control and reward-based learning, and is thus emerging as a novel drug target for CNS disorders including schizophrenia, Parkinson's disease, anxiety and addiction...
December 12, 2018: ACS Chemical Neuroscience
Wei-Ze Syu, Shyi-Gen Chen, James Yi-Hsin Chan, Chih-Hsin Wang, Niann-Tzyy Dai, Shih-Ming Huang
INTRODUCTION: Reconstruction of segmental peripheral nerve gap is still challenging when the autografts are unavailable owing to limited availability of donor site and functional recovery. The creation of artificial conduits composed of biological or synthetic materials is still developing. Acellular dermal matrix (ADM) has been widely studied and its extension and plasticity properties may become suitable nerve conduits under different forms of nerve gaps. Adipose-derived stem cells (ADSCs) have the potential to differentiate into various cell types of different germ layers including neural stem cells (NSCs)...
January 2019: Annals of Plastic Surgery
Sebastian Brickel, Markus Meuwly
The Claisen rearrangement is a carbon-carbon bond-forming, pericyclic reaction of fundamental importance due to its relevance in synthetic and mechanistic investigations of organic and biological chemistry. Despite continued efforts, the molecular origins of the rate acceleration in going from the aqueous phase into the protein is still incompletely understood. In the present work the rearrangement reaction for allyl-vinyl-ether (AVE), its dicarboxylated variant (AVE-(CO2 )2 ) and the biologically relevant substrate chorismate is investigated in gas phase, water and in chorismate mutase...
December 12, 2018: Journal of Physical Chemistry. B
Eun-Sun Kim, Hongjun Jang, Sun-Young Chang, Seung-Hoon Baek, Ok-Nam Bae, Hyoungsu Kim
A concise synthesis of sericetin (1) was performed in four steps from readily available 3- O-benzylgalangin (4), featuring electrocyclization to produce the tricyclic core and a sequential aromatic Claisen/Cope rearrangement to incorporate the 8-prenyl group of 1. In addition, the therapeutic potential of sericetin (1), isosericetin (2), and three prenylated tetracyclic synthetic intermediates (11, 12, and 14) against cisplatin-induced nephrotoxicity using renal tubular cells were evaluated. Compound 14 showed therapeutic potential against cisplatin-induced kidney damage...
December 12, 2018: Journal of Natural Products
Salman Khan, Khurshid Ahmad, Ajaz Ahmad, Mohammad Raish, Basit L Jan, Altaf Khan, Mohd Sajid Khan
Background: Biological synthesis of nanomaterials possesses unprecedented potential in the production of nanomaterials due to their ability to produce nanomaterials with improved biocompatibility in addition to eco-friendly synthetic procedures. Methods: This article reports the isolation of an air-borne fungus from the campus of Integral University, Lucknow, with an exceptional ability to withstand very high concentrations of silver salt. The fungus was found to produce pentagonal silver nanoparticles (AgPgNps) when silver ions were reduced from silver nitrate...
2018: International Journal of Nanomedicine
Joshua Heyza, Wen Lei, Donovan Watza, Hao Zhang, Wei Chen, Jessica B Back, Ann G Schwartz, Gerold Bepler, Steve M Patrick
PURPOSE: ERCC1/XPF is a DNA endonuclease with variable expression in primary tumor specimens, and has been investigated as a predictive biomarker for efficacy of platinum-based chemotherapy. The failure of clinical trials utilizing ERCC1 expression to predict response to platinum-based chemotherapy suggests additional mechanisms underlying the basic biology of ERCC1 in the response to interstrand crosslinks (ICLs) remain unknown. We aimed to characterize a panel of ERCC1 knockout (D) cell lines where we identified a synthetic viable phenotype in response to ICLs with ERCC1 deficiency...
December 11, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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