scholarly journals Cellular uptake of aptamer by Quantum Dots (QDs)

2018 ◽  
Vol 1 (1) ◽  
pp. 01-01
Author(s):  
Haleena Kaur
Keyword(s):  
Binding Affinity ◽  
Biological Fluids ◽  
High Specificity ◽  
Binding Domain ◽  
Dna Aptamer ◽  
Heparin Binding ◽  
Stem Loop ◽  
Diagnostic Potential ◽  
Phosphate Backbone ◽  
Aptamer Sequence

Aptamers are short single stranded oligonucleotide sequences that exhibit high binding affinity and high specificity against their target molecule. Binding affinity and specificity are crucial features for aptamers in order to exploit their therapeutic and diagnostic potential and to make them an appealing candidate for the commercial market1,2. Aptamers contain functional moieties that can fold into different conformation such as hairpin stem and loops, G-quadruplexes, and pseudoknots. A study led by Dr Harleen Kaur involving unique stem-loop truncation strategy was employed to find the binding domain in a 66-mer long DNA aptamer sequence against the heparin binding domain of vascular endothelial growth factor (VEGF165) protein1. The results from the work demonstrated identification of a 26-mer long aptamer sequence referred as SL2-B in the paper with improvement in the binding affinity by more than 200-folds (Kd = 0.5nM) against VEGF protein. To improve the biostability of the aptamer in the biological fluids, the phosphorothioate linkages (PS-linkages) in the phosphate backbone of the DNA were introduced at the 5’-and 3’-termini of the obtained SL2-B aptamer sequence. The PS-modified SL2-B aptamer sequence demonstrated significant improvement in the stability without comprising

Limited Proteolysis of Vitronectin by Plasmin Destroys Heparin Binding Activity

1991 ◽  
Vol 66 (03) ◽  
pp. 310-314 ◽  
Author(s):  
David C Sane ◽  
Tammy L Moser ◽  
Charles S Greenberg
Keyword(s):  
Limited Proteolysis ◽  
Plasminogen Activator Inhibitor ◽  
Binding Activity ◽  
Binding Domain ◽  
Heparin Binding ◽  
Inhibitor Type ◽  
Activator Inhibitor Type ◽  
Activator Inhibitor ◽  
Pai 1

SummaryVitronectin (VN) stabilizes plasminogen activator inhibitor type 1 (PAI-1) activity and prevents the fibrin(ogen)-induced acceleration of plasminogen activation by t-PA. These antifibrinolytic activities as well as other functions are mediated by the glycosaminoglycan (GAG) binding domain of VN. Since the GAG binding region is rich in arginyl and lysyl residues, it is a potential target for enzymes such as plasmin. In this paper, the dose and time-dependent proteolysis of VN by plasmin is demonstrated. The addition of urokinase or streptokinase (200 units/ml) to plasma also produced proteolysis of VN. With minimal proteolysis, the 75 kDa band was degraded to a 62-65 kDa form of VN. This minimal proteolysis destroyed the binding of [3H]-heparin to VN and reversed the neutralization of heparin by VN.Thus, the plasmin-mediated proteolysis of the GAG binding activity of VN could destroy the antifibrinolytic activity of VN during physiologic conditions and during thrombolytic therapy. Furthermore, other functions of VN in complement and coagulation systems that are mediated by the GAG binding domain may be destroyed by plasmin proteolysis.

Distinct Modulation of Wild-Type and Selective Gene Mutated Vitamin D Receptor by Essential Poly Unsaturated Fatty Acids

2021 ◽  
Vol 21 ◽  
Author(s):  
Hari Balaji ◽  
Selvaraj Ayyamperuma ◽  
Niladri Saha ◽  
Shyam Sundar Pottabathula ◽  
Jubie Selvaraj ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Vitamin D ◽  
Ligand Binding ◽  
Vitamin D Deficiency ◽  
Binding Affinity ◽  
Unsaturated Fatty Acids ◽  
Binding Domain ◽  
Ligand Binding Domain ◽  
Binding Energies ◽  
Wild Type

: Vitamin-D deficiency is a global concern. Gene mutations in the vitamin D receptor’s (VDR) ligand binding domain (LBD) variously alter the ligand binding affinity, heterodimerization with retinoid X receptor (RXR) and inhibit coactivator interactions. These LBD mutations may result in partial or total hormone unresponsiveness. A plethora of evidence report that selective long chain polyunsaturated fatty acids (PUFAs) including eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and arachidonic acid (AA) bind to the ligand-binding domain of VDR and lead to transcriptional activation. We therefore hypothesize that selective PUFAs would modulate the dynamics and kinetics of VDRs, irrespective bioactive of vitamin-D binding. The spatial arrangements of the selected PUFAs in VDR active site were examined by in-silico docking studies. The docking results revealed that PUFAs have fatty acid structure-specific binding affinity towards VDR. The calculated EPA, DHA & AA binding energies (Cdocker energy) were lesser compared to vitamin-D in wild type of VDR (PDB id: 2ZLC). Of note, the DHA has higher binding interactions to the mutated VDR (PDB id: 3VT7) when compared to the standard Vitamin-D. Molecular dynamic simulation was utilized to confirm the stability of potential compound binding of DHA with mutated VDR complex. These findings suggest the unique roles of PUFAs in VDR activation and may offer alternate strategy to circumvent vitamin-D deficiency.

Nuclease Hydrolysis Does Not Drive the Rapid Signaling Decay of DNA Aptamer-Based Electrochemical Sensors in Biological Fluids

Langmuir ◽  
2021 ◽  
Vol 37 (17) ◽  
pp. 5213-5221
Author(s):  
Alexander Shaver ◽  
Nandini Kundu ◽  
Brian E. Young ◽  
Philip A. Vieira ◽  
Jonathan T. Sczepanski ◽  
...  
Keyword(s):  
Electrochemical Sensors ◽  
Biological Fluids ◽  
Dna Aptamer ◽  
Rapid Signaling

scholarly journals Long Non-Coding RNAs (lncRNAs) in Cardiovascular Disease Complication of Type 2 Diabetes

Diagnostics ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 145
Author(s):  
Nurruzanna Ismail ◽  
Noraidatulakma Abdullah ◽  
Nor Azian Abdul Murad ◽  
Rahman Jamal ◽  
Siti Aishah Sulaiman
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Risk Factor ◽  
Disease Progression ◽  
Biological Fluids ◽  
Specific Cell ◽  
New Paradigm ◽  
Diagnostic Potential ◽  
Non Coding Rnas

The discovery of non-coding RNAs (ncRNAs) has opened a new paradigm to use ncRNAs as biomarkers to detect disease progression. Long non-coding RNAs (lncRNA) have garnered the most attention due to their specific cell-origin and their existence in biological fluids. Type 2 diabetes patients will develop cardiovascular disease (CVD) complications, and CVD remains the top risk factor for mortality. Understanding the lncRNA roles in T2D and CVD conditions will allow the future use of lncRNAs to detect CVD complications before the symptoms appear. This review aimed to discuss the roles of lncRNAs in T2D and CVD conditions and their diagnostic potential as molecular biomarkers for CVD complications in T2D.

scholarly journals Targeting exosites on blood coagulation proteases

2005 ◽  
Vol 77 (2) ◽  
pp. 275-280 ◽  
Author(s):  
Robson Q. Monteiro
Keyword(s):  
Blood Coagulation ◽  
High Specificity ◽  
Heparin Binding ◽  
Zymogen Activation ◽  
Prothrombinase Complex ◽  
Blood Sucking ◽  
Anticoagulant Drugs ◽  
Coagulation Inhibitors ◽  
Tissue Factor Pathway ◽  
Surface Domains

The high specificity of blood coagulation proteases has been attributed not only to residues surrounding the active site but also to other surface domains that are involved in recognizing and interacting with macromolecular substrates and inhibitors. Specific blood coagulation inhibitors obtained from exogenous sources such as blood sucking salivary glands and snake venoms have been identified. Some of these inhibitors interact with exosites on coagulation enzymes. Two examples are discussed in this short revision. Bothrojaracin is a snake venom-derived protein that binds to thrombin exosites 1 and 2. Complex formation impairs several exosite-dependent activities of thrombin including fibrinogen cleavage and platelet activation. Bothrojaracin also interacts with proexosite 1 on prothrombin thus decreasing the zymogen activation by the prothrombinase complex (FXa/FVa). Ixolaris is a two Kunitz tick salivary gland inhibitor, that is homologous to tissue factor pathway inhibitor. Recently it was demonstrated that ixolaris binds to heparin-binding exosite of FXa, thus impairing the recognition of prothrombin by the enzyme. In addition, ixolaris interacts with FX possibly through the heparin-binding proexosite. Differently from FX, the ixolaris-FX complex is not recognized as substrate by the intrinsic tenase complex (FIXa/FVIIIa). We conclude that these inhibitors may serve as tools for the study of coagulation exosites as well as prototypes for new anticoagulant drugs.

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