Rational Design of an Artificial Nuclease by Engineering a Hetero-Dinuclear Center of Mg-Heme in Myoglobin

ACS Catalysis ◽  
2020 ◽  
Vol 10 (24) ◽  
pp. 14359-14365
Author(s):  
Jie Luo ◽  
Ke-Jie Du ◽  
Hong Yuan ◽  
Chuan-Wan Wei ◽  
Jia-Jia Lang ◽  
...  
Keyword(s):  
Rational Design ◽  
Artificial Nuclease

scholarly journals Integrative Analysis of CRISPR/Cas9 Target Sites in the HumanHBBGene

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Yumei Luo ◽  
Detu Zhu ◽  
Zhizhuo Zhang ◽  
Yaoyong Chen ◽  
Xiaofang Sun
Keyword(s):  
Rational Design ◽  
Disease Modeling ◽  
Globin Gene ◽  
Transcriptional Factor ◽  
Coding Regions ◽  
Crispr System ◽  
Target Sites ◽  
Artificial Nuclease ◽  
Target Effects ◽  
Target Sets

Recently, the clustered regularly interspaced short palindromic repeats (CRISPR) system has emerged as a powerful customizable artificial nuclease to facilitate precise genetic correction for tissue regeneration and isogenic disease modeling. However, previous studies reported substantial off-target activities of CRISPR system in human cells, and the enormous putative off-target sites are labor-intensive to be validated experimentally, thus motivating bioinformatics methods for rational design of CRISPR system and prediction of its potential off-target effects. Here, we describe an integrative analytical process to identify specific CRISPR target sites in the humanβ-globin gene (HBB) and predict their off-target effects. Our method includes off-target analysis in both coding and noncoding regions, which was neglected by previous studies. It was found that the CRISPR target sites in the introns have fewer off-target sites in the coding regions than those in the exons. Remarkably, target sites containing certain transcriptional factor motif have enriched binding sites of relevant transcriptional factor in their off-target sets. We also found that the intron sites have fewer SNPs, which leads to less variation of CRISPR efficiency in different individuals during clinical applications. Our studies provide a standard analytical procedure to select specific CRISPR targets for genetic correction.

Molecular insights on the dynamic stability of peptide nucleic acid functionalized carbon and boron nitride nanotubes

2021 ◽  
Vol 23 (1) ◽  
pp. 219-228
Author(s):  
Nabanita Saikia ◽  
Mohamed Taha ◽  
Ravindra Pandey
Keyword(s):  
Nucleic Acid ◽  
Boron Nitride ◽  
Nucleic Acids ◽  
Dynamic Stability ◽  
Peptide Nucleic Acid ◽  
Rational Design ◽  
Peptide Nucleic Acids ◽  
Boron Nitride Nanotubes ◽  
Molecular Hybrids ◽  
Single Wall Nanotubes

The rational design of self-assembled nanobio-molecular hybrids of peptide nucleic acids with single-wall nanotubes rely on understanding how biomolecules recognize and mediate intermolecular interactions with the nanomaterial's surface.

Optimizing electron density of nickel sulfide electrocatalysts through sulfur vacancy engineering for alkaline hydrogen evolution

2020 ◽  
Vol 8 (35) ◽  
pp. 18207-18214
Author(s):  
Dongbo Jia ◽  
Lili Han ◽  
Ying Li ◽  
Wenjun He ◽  
Caichi Liu ◽  
...  
Keyword(s):  
Hydrogen Evolution ◽  
Electron Density ◽  
Rational Design ◽  
Nickel Sulfide ◽  
Catalytic Performance ◽  
Sulfide Catalysts ◽  
Sulfur Vacancy

A novel, rational design for porous S-vacancy nickel sulfide catalysts with remarkable catalytic performance for alkaline HER.

Rational design of annotine analogues with increased inhibitory activity towards acetylcholinesterase

Planta Medica ◽  
2016 ◽  
Vol 81 (S 01) ◽  
pp. S1-S381
Author(s):  
ES Halldorsdottir ◽  
S Oddsson ◽  
AM Einarsdottir ◽  
B Eiriksdottir ◽  
NM Kowal ◽  
...  
Keyword(s):  
Inhibitory Activity ◽  
Rational Design

Anticoagulant Activity of Hirulog™, a Direct Thrombin Inhibitor, in Humans

1993 ◽  
Vol 69 (02) ◽  
pp. 157-163 ◽  
Author(s):  
Irving Fox ◽  
Adrian Dawson ◽  
Peter Loynds ◽  
Jane Eisner ◽  
Kathleen Findlen ◽  
...  
Keyword(s):  
Rational Design ◽  
Therapeutic Potential ◽  
Anticoagulant Activity ◽  
Subcutaneous Administration ◽  
Direct Thrombin Inhibitor ◽  
Controlled Study ◽  
Thrombin Inhibitor ◽  
Thrombin Time ◽  
Thrombotic Disease ◽  
Dose Dependent

SummaryHirulog™ (BG8967) is a direct thrombin inhibitor built by rational design using the protein hirudin as a model (Maraganore et al. [1990]; Biochemistry 29: 7095–101). In order to evaluate the therapeutic potential for hirulog in the management of thrombotic disease, the tolerability and anticoagulant activity of the agent were examined in a study of human volunteers.In a randomized, placebo-controlled study (n = 54), the intravenous infusion of hirulog over 15 min showed a rapid, dose-dependent prolongation of activated partial thromboplastin time (APTT), prothrombin time (PT), and thrombin time (TT). There was a corresponding dose-dependent increase in plasma hirulog levels. The peptide was rapidly cleared with a half-life of 36 min and a total body clearance rate for the peptide of 0.43 1 kg−1 h−1. Similar activity was observed following subcutaneous injection but with sustained pharmacodynamic and pharmacokinetic behavior. There was a significant correlation between pharmacokinetic and pharmacodynamic variables for both intravenous (r = 0.8, p <0.001) and subcutaneous administration (r = 0.7, p = 0.002).To evaluate the possible interactions of aspirin on the tolerability and anticoagulant activity of intravenous hirulog, a cross-over design was employed in eight subjects. Aspirin administration did not modify the peptide’s activity. At the administered dose of 0.6 mg kg−1 h−1 for 2 h, hirulog infusion prolonged APTT from 230 to 260% baseline. The infusion of hirulog in subjects who had received aspirin was not associated with any significant changes in the template bleeding time.The final phase of the study examined the activity and tolerability of hirulog in ten subjects during prolonged intravenous infusions for up to 24 h. The peptide (0.3 mg kg−1 h−1) exhibited sustained anticoagulant activity with no evidence for a cumulative effect. During hirulog infusion, APTT was prolonged from 210 to 250% baseline.In all phases of the study, hirulog administration was generally well-tolerated.Our observations show that hirulog is an active antithrombin agent with excellent tolerability in humans. As a direct thrombin inhibitor, hirulog provides a novel approach for the management of thrombotic disease.

Development of a rational design methodology for precast concrete slender spandrel beams: Part 1, experimental results

PCI Journal ◽  
2011 ◽  
Vol 56 (2) ◽  
pp. 88-112 ◽  
Author(s):  
Gregory Lucier ◽  
Catrina Walter ◽  
Sami Rizkalla ◽  
Paul Zia ◽  
Gary Klein
Keyword(s):  
Design Methodology ◽  
Rational Design ◽  
Precast Concrete ◽  
Experimental Results

DNA Inspirited Rational Construction of Nonconventional Luminophores with Efficient and Color-Tunable Afterglow

2020 ◽  
Author(s):  
Yunzhong Wang ◽  
Saixing Tang ◽  
Yating Wen ◽  
Shuyuan Zheng ◽  
Bing Yang ◽  
...  
Keyword(s):  
Rational Design ◽  
Room Temperature ◽  
Double Helix ◽  
Mechanical Grinding ◽  
Room Temperature Phosphorescence ◽  
Color Tunable ◽  
Potential Applications ◽  
Rational Construction ◽  
Double Helix Structure ◽  
Made In

<div>Persistent room-temperature phosphorescence (p-RTP) from pure organics is attractive </div><div>due to its fundamental importance and potential applications in molecular imaging, </div><div>sensing, encryption, anticounterfeiting, etc.1-4 Recently, efforts have been also made in </div><div>obtaining color-tunable p-RTP in aromatic phosphors5 and nonconjugated polymers6,7. </div><div>The origin of color-tunable p-RTP and the rational design of such luminogens, </div><div>particularly those with explicit structure and molecular packing, remain challenging. </div><div>Noteworthily, nonconventional luminophores without significant conjugations generally </div><div>possess excitation-dependent photoluminescence (PL) because of the coexistence of </div><div>diverse clustered chromophores6,8, which strongly implicates the possibility to achieve </div><div>color-tunable p-RTP from their molecular crystals assisted by effective intermolecular </div><div>interactions. Here, inspirited by the highly stable double-helix structure and multiple </div><div>hydrogen bonds in DNA, we reported a series of nonconventional luminophores based on </div><div>hydantoin (HA), which demonstrate excitation-dependent PL and color-tunable p-RTP </div><div>from sky-blue to yellowish-green, accompanying unprecedentedly high PL and p-RTP </div><div>efficiencies of up to 87.5% and 21.8%, respectively. Meanwhile, the p-RTP emissions are </div><div>resistant to vigorous mechanical grinding, with lifetimes of up to 1.74 s. Such robust, </div><div>color-tunable and highly efficient p-RTP render the luminophores promising for varying </div><div>applications. These findings provide mechanism insights into the origin of color-tunable </div><div>p-RTP, and surely advance the exploitation of efficient nonconventional luminophores.</div>

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