ChemInform Abstract: Recent Developments in the Rational Design of Multivalent Glycoconjugates

ChemInform ◽  
2010 ◽  
Vol 28 (34) ◽  
pp. no-no
Author(s):  
R. ROY
Keyword(s):  
Rational Design ◽  
Recent Developments

scholarly journals Endogenous and exogenous electric fields as modifiers of brain activity: rational design of noninvasive brain stimulation with transcranial alternating current stimulation

2014 ◽  
Vol 16 (1) ◽  
pp. 93-102 ◽  
Keyword(s):  
Electric Fields ◽  
Brain Stimulation ◽  
Rational Design ◽  
Brain Activity ◽  
Field Potential ◽  
Alternating Current ◽  
Noninvasive Brain Stimulation ◽  
Starting Point ◽  
Recent Developments ◽  
Transcranial Alternating Current Stimulation

Synchronized neuronal activity in the cortex generates weak electric fields that are routinely measured in humans and animal models by electroencephalography and local field potential recordings. Traditionally, these endogenous electric fields have been considered to be an epiphenomenon of brain activity. Recent work has demonstrated that active cortical networks are surprisingly susceptible to weak perturbations of the membrane voltage of a large number of neurons by electric fields. Simultaneously, noninvasive brain stimulation with weak, exogenous electric fields (transcranial current stimulation, TCS) has undergone a renaissance due to the broad scope of its possible applications in modulating brain activity for cognitive enhancement and treatment of brain disorders. This review aims to interface the recent developments in the study of both endogenous and exogenous electric fields, with a particular focus on rhythmic stimulation for the modulation of cortical oscillations. The main goal is to provide a starting point for the use of rational design for the development of novel mechanism-based TCS therapeutics based on transcranial alternating current stimulation, for the treatment of psychiatric illnesses.

Metalloligand Strategies for Assembling Heteronuclear Nanocages – Recent Developments

2019 ◽  
Vol 72 (10) ◽  
pp. 731 ◽  
Author(s):  
Feng Li ◽  
Leonard F. Lindoy
Keyword(s):  
Structural Properties ◽  
Metal Ion ◽  
Rational Design ◽  
Building Blocks ◽  
Structural Elements ◽  
Present Discussion ◽  
The Past ◽  
Recent Developments ◽  
Metal Organic ◽  
Multifunctional Ligand

The use of metalloligands as building blocks for the assembly of metallo-organic cages has received increasing attention over the past two decades or so. In part, the popularity of this approach reflects its stepwise nature that lends itself to the predesigned construction of metallocages and especially heteronuclear metallocages. The focus of the present discussion is on the use of metalloligands for the construction of discrete polyhedral cages, very often incorporating heterometal ions as structural elements. The metalloligand approach uses metal-bound multifunctional ligand building blocks that display predesigned structural properties for coordination to a second metal ion such that the rational design and construction of both homo- and heteronuclear metal–organic cages are facilitated. The present review covers published literature in the area from early 2015 to early 2019.

scholarly journals The Bewildering Antitubercular Action of Pyrazinamide

2020 ◽  
Vol 84 (2) ◽  
Author(s):  
Elise A. Lamont ◽  
Nicholas A. Dillon ◽  
Anthony D. Baughn
Keyword(s):  
Mode Of Action ◽  
Rational Design ◽  
Multidrug Resistant ◽  
Future Research ◽  
Therapeutic Approaches ◽  
Treatment Regimens ◽  
Tb Treatment ◽  
Short Course ◽  
Recent Developments ◽  
Susceptibility And Resistance

SUMMARY Pyrazinamide (PZA) is a cornerstone antimicrobial drug used exclusively for the treatment of tuberculosis (TB). Due to its ability to shorten drug therapy by 3 months and reduce disease relapse rates, PZA is considered an irreplaceable component of standard first-line short-course therapy for drug-susceptible TB and second-line treatment regimens for multidrug-resistant TB. Despite over 60 years of research on PZA and its crucial role in current and future TB treatment regimens, the mode of action of this unique drug remains unclear. Defining the mode of action for PZA will open new avenues for rational design of novel therapeutic approaches for the treatment of TB. In this review, we discuss the four prevailing models for PZA action, recent developments in modulation of PZA susceptibility and resistance, and outlooks for future research and drug development.

scholarly journals Recent advances in the rational synthesis and self-assembly of anisotropic plasmonic nanoparticles

2018 ◽  
Vol 90 (9) ◽  
pp. 1393-1407 ◽  
Author(s):  
Leonardo Scarabelli
Keyword(s):  
Self Assembly ◽  
Rational Design ◽  
Short Review ◽  
Cascade Reactions ◽  
Full Potential ◽  
Plasmonic Materials ◽  
Optical And Electronic Properties ◽  
Complex Architectures ◽  
Recent Developments ◽  
Surface Chemistries

Abstract The field of plasmonics has grown at an incredible pace in the last couple of decades, and the synthesis and self-assembly of anisotropic plasmonic materials remains highly dynamic. The engineering of nanoparticle optical and electronic properties has resulted in important consequences for several scientific fields, including energy, medicine, biosensing, and electronics. However, the full potential of plasmonics has not yet been realized due to crucial challenges that remain in the field. In particular, the development of nanoparticles with new plasmonic properties and surface chemistries could enable the rational design of more complex architectures capable of performing advanced functions, like cascade reactions, energy conversion, or signal transduction. The scope of this short review is to highlight the most recent developments in the synthesis and self-assembly of anisotropic metal nanoparticles, which are capable of bringing forward the next generation of plasmonic materials.

Well-defined two dimensional covalent organic polymers: rational design, controlled syntheses, and potential applications

2015 ◽  
Vol 6 (11) ◽  
pp. 1896-1911 ◽  
Author(s):  
Zhonghua Xiang ◽  
Dapeng Cao ◽  
Liming Dai
Keyword(s):  
Rational Design ◽  
Two Dimensional ◽  
Organic Polymers ◽  
Design Synthesis ◽  
Recent Developments ◽  
Potential Applications

Recent developments in the design, synthesis and application of 2D covalent organic polymers are reviewed, along with some perspectives and challenges.

scholarly journals Short Peptides in Minimalistic Biocatalyst Design

Biocatalysis ◽  
2015 ◽  
Vol 1 (1) ◽  
pp. 67-81 ◽  
Author(s):  
Krystyna L. Duncan ◽  
Rein V. Ulijn
Keyword(s):  
Active Sites ◽  
Rational Design ◽  
Similar Rate ◽  
Ester Hydrolysis ◽  
Peptide Sequence ◽  
Short Peptides ◽  
Significant Progress ◽  
Fundamental Understanding ◽  
Recent Developments ◽  
Binding Pockets

AbstractWe review recent developments in the use of short peptides in the design of minimalistic biocatalysts focusing on ester hydrolysis. A number of designed peptide nanostructures are shown to have (modest) catalytic activity. Five features are discussed and illustrated by literature examples, including primary peptide sequence, nanosurfaces/scaffolds, binding pockets, multivalency and the presence of metal ions. Some of these are derived from natural enzymes, but others, such as multivalency of active sites on designed nanofibers, may give rise to new features not found in natural enzymes. Remarkably, it is shown that each of these design features give rise to similar rate enhancements in ester hydrolysis. Overall, there has been significant progress in the development of fundamental understanding of the factors that influence binding and activity in recent years, holding promise for increasingly rational design of peptide based biocatalysts.

scholarly journals Bacterial cytochrome P450-catalyzed regio- and stereoselective steroid hydroxylation enabled by directed evolution and rational design

2020 ◽  
Vol 7 (1) ◽  
Author(s):  
Xiaodong Zhang ◽  
Yaqin Peng ◽  
Jing Zhao ◽  
Qian Li ◽  
Xiaojuan Yu ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Biological Activity ◽  
Cytochrome P450 ◽  
Directed Evolution ◽  
Rational Design ◽  
Cytochrome P450s ◽  
Steroid Hydroxylation ◽  
Recent Developments ◽  
Low Activity ◽  
High Expression Level

AbstractSteroids are the most widely marketed products by the pharmaceutical industry after antibiotics. Steroid hydroxylation is one of the most important functionalizations because their derivatives enable a higher biological activity compared to their less polar non-hydroxylated analogs. Bacterial cytochrome P450s constitute promising biocatalysts for steroid hydroxylation due to their high expression level in common workhorses like Escherichia coli. However, they often suffer from wrong or insufficient regio- and/or stereoselectivity, low activity, narrow substrate range as well as insufficient thermostability, which hampers their industrial application. Fortunately, these problems can be generally solved by protein engineering based on directed evolution and rational design. In this work, an overview of recent developments on the engineering of bacterial cytochrome P450s for steroid hydroxylation is presented.

Electromigration Damage in Conductor Lines: Recent Progress in Microscopic Observation and Mechanistic Modelling

1994 ◽  
Vol 338 ◽  
Author(s):  
E. Arzt ◽  
O. Kraft ◽  
U.E. MÖckl
Keyword(s):  
Rational Design ◽  
Recent Progress ◽  
Ex Situ ◽  
Mechanistic Modelling ◽  
Stress Effects ◽  
Recent Developments ◽  
Current Densities ◽  
Damage Map ◽  
Shape Changes

ABSTRACTIn this paper an overview of recent developments in understanding electromigration damage mechanisms is given. Based on our detailed studies, both ex-situ and in-situ, of damage in unpassivated near-bamboo lines, we develop a theoretical electromigration damage map. It explains why “slit-like” failure becomes predominant for narrow lines and low current densities. The mechanism of slit formation is discussed in the light of new analytical and numerical simulations of pore shape changes, which take stress effects into account. Possible implications for the rational design of improved metallization alloys are suggested.

scholarly journals Nucleic Acid–Based Therapeutics in Orphan Neurological Disorders: Recent Developments

2021 ◽  
Vol 8 ◽  
Author(s):  
Olga Khorkova ◽  
Jane Hsiao ◽  
Claes Wahlestedt
Keyword(s):  
Nucleic Acid ◽  
Neurological Disorders ◽  
Rational Design ◽  
Neurological Diseases ◽  
Clinical Stage ◽  
Genetic Research ◽  
Orphan Disease ◽  
Common Disease ◽  
Orphan Diseases ◽  
Recent Developments

The possibility of rational design and the resulting faster and more cost-efficient development cycles of nucleic acid–based therapeutics (NBTs), such as antisense oligonucleotides, siRNAs, and gene therapy vectors, have fueled increased activity in developing therapies for orphan diseases. Despite the difficulty of delivering NBTs beyond the blood–brain barrier, neurological diseases are significantly represented among the first targets for NBTs. As orphan disease NBTs are now entering the clinical stage, substantial efforts are required to develop the scientific background and infrastructure for NBT design and mechanistic studies, genetic testing, understanding natural history of orphan disorders, data sharing, NBT manufacturing, and regulatory support. The outcomes of these efforts will also benefit patients with “common” diseases by improving diagnostics, developing the widely applicable NBT technology platforms, and promoting deeper understanding of biological mechanisms that underlie disease pathogenesis. Furthermore, with successes in genetic research, a growing proportion of “common” disease cases can now be attributed to mutations in particular genes, essentially extending the orphan disease field. Together, the developments occurring in orphan diseases are building the foundation for the future of personalized medicine. In this review, we will focus on recent achievements in developing therapies for orphan neurological disorders.

scholarly journals Synergistic optimisation of expression, folding, and secretion improves E. coli AppA phytase production in Pichia pastoris

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Laura Navone ◽  
Thomas Vogl ◽  
Pawarisa Luangthongkam ◽  
Jo-Anne Blinco ◽  
Carlos Luna-Flores ◽  
...  
Keyword(s):  
Pichia Pastoris ◽  
Rational Design ◽  
Alternative Pathway ◽  
Cost Effective ◽  
Global Market ◽  
Microbial Production ◽  
Phytase Production ◽  
E Coli ◽  
Industrial Manufacture ◽  
Recent Developments

Abstract Background Pichia pastoris (Komagataella phaffii) is an important platform for heterologous protein production due to its growth to high cell density and outstanding secretory capabilities. Recent developments in synthetic biology have extended the toolbox for genetic engineering of P. pastoris to improve production strains. Yet, overloading the folding and secretion capacity of the cell by over-expression of recombinant proteins is still an issue and rational design of strains is critical to achieve cost-effective industrial manufacture. Several enzymes are commercially produced in P. pastoris, with phytases being one of the biggest on the global market. Phytases are ubiquitously used as a dietary supplement for swine and poultry to increase digestibility of phytic acid, the main form of phosphorous storage in grains. Results Potential bottlenecks for expression of E. coli AppA phytase in P. pastoris were explored by applying bidirectional promoters (BDPs) to express AppA together with folding chaperones, disulfide bond isomerases, trafficking proteins and a cytosolic redox metabolism protein. Additionally, transcriptional studies were used to provide insights into the expression profile of BDPs. A flavoprotein encoded by ERV2 that has not been characterised in P. pastoris was used to improve the expression of the phytase, indicating its role as an alternative pathway to ERO1. Subsequent AppA production increased by 2.90-fold compared to the expression from the state of the AOX1 promoter. Discussion The microbial production of important industrial enzymes in recombinant systems can be improved by applying newly available molecular tools. Overall, the work presented here on the optimisation of phytase production in P. pastoris contributes to the improved understanding of recombinant protein folding and secretion in this important yeast microbial production host.

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