scholarly journals Aptasensors for Small Molecule Detection

2012 ◽  
Vol 67 (10) ◽  
pp. 976-986 ◽  
Author(s):  
Johanna-Gabriela Walter ◽  
Alexandra Heilkenbrinker ◽  
Jonas Austerjost ◽  
Suna Timur ◽  
Frank Stahl ◽  
...  
Keyword(s):  
Molecular Recognition ◽  
Small Molecules ◽  
Small Molecule ◽  
Conformational Changes ◽  
Design Strategies ◽  
Intelligent Sensors ◽  
Biological Recognition ◽  
Recognition Elements ◽  
Small Molecule Detection

Aptamers are single-stranded oligonucleotides composed of RNA or DNA that are able to bind their corresponding targets via molecular recognition. Thus, aptamers can be thought of as nucleic acidbased alternatives to antibodies and have attracted attention as receptors in biosensors. Aptamers seem to be ideal biological recognition elements, since they enable the design of intelligent sensors based on their specific properties. Especially the fact that most aptamers undergo conformational changes during the binding of the target and their oligonucleotide nature can be used to rationally design novel sensing strategies. This review focuses on aptasensors for the detection of small molecules. In the first part, aptamers, their generation and their properties are briefly described. In the second part, different design strategies for aptasensors are reviewed, and examples for the detection of small molecules are given.

scholarly journals Challenges and Opportunities for Small Molecule Aptamer Development

2012 ◽  
Vol 2012 ◽  
pp. 1-20 ◽  
Author(s):  
Maureen McKeague ◽  
Maria C. DeRosa
Keyword(s):  
Molecular Recognition ◽  
Small Molecules ◽  
Small Molecule ◽  
Chemical Biology ◽  
Biological Functions ◽  
High Affinity ◽  
Challenges And Opportunities ◽  
Recognition Elements ◽  
Technical Challenges ◽  
Viable Approach

Aptamers are single-stranded oligonucleotides that bind to targets with high affinity and selectivity. Their use as molecular recognition elements has emerged as a viable approach for biosensing, diagnostics, and therapeutics. Despite this potential, relatively few aptamers exist that bind to small molecules. Small molecules are important targets for investigation due to their diverse biological functions as well as their clinical and commercial uses. Novel, effective molecular recognition probes for these compounds are therefore of great interest. This paper will highlight the technical challenges of aptamer development for small molecule targets, as well as the opportunities that exist for their application in biosensing and chemical biology.

scholarly journals A Simple Displacement Aptamer Assay on Resistive Pulse Sensor for Small Molecule Detection

2020 ◽  
Author(s):  
Rhushabh Maugi ◽  
bernadette gamble ◽  
david bunka ◽  
Mark Platt
Keyword(s):  
Small Molecules ◽  
Small Molecule ◽  
Label Free ◽  
Resistive Pulse ◽  
Pulse Sensor ◽  
Label Free Detection ◽  
Ssdna Aptamer ◽  
Aptamer Assay ◽  
Small Molecule Detection ◽  
Surface Changes

A universal aptamer-based sensing strategy is proposed using DNA modified nanocarriers and Resistive Pulse Sensing for the rapid and label free detection of small molecules. The surface of a magnetic nanocarrier was first modified with a ssDNA aka linker which is designed to be partially complimentary in sequence to a ssDNA aptamer. The aptamer and linker form a stable dsDNA complex on the nanocarriers surface. Upon the addition of the target molecule, a conformational change takes place where the aptamer preferentially binds to the target over the linker; causing the aptamer to be released into solution. The RPS measures the change in velocity of the nanocarrier as its surface changes from dsDNA to ssDNA, and its velocity is used as a proxy for the concentration of the target. We illustrate the versatility of the assay by demonstrating the detection of the antibiotic Moxifloxacin, and chemotherapeutics Imatinib and Irinotecan.

scholarly journals Application of high-throughput screening to identify a novel αIIb-specific small- molecule inhibitor of αIIbβ3-mediated platelet interaction with fibrinogen

Blood ◽  
2008 ◽  
Vol 111 (3) ◽  
pp. 1248-1256 ◽  
Author(s):  
Robert Blue ◽  
Marta Murcia ◽  
Charles Karan ◽  
Markéta Jiroušková ◽  
Barry S. Coller
Keyword(s):  
Small Molecules ◽  
Small Molecule ◽  
Conformational Changes ◽  
High Throughput Screening ◽  
Metal Ion ◽  
Selective Inhibition ◽  
Docking Simulations ◽  
Fibrinogen Binding ◽  
Molecule Inhibitor ◽  
Novel Structures

AbstractSmall-molecule αIIbβ3 antagonists competitively block ligand binding by spanning between the D224 in αIIb and the MIDAS metal ion in β3. They variably induce conformational changes in the receptor, which may have undesirable consequences. To identify αIIbβ3 antagonists with novel structures, we tested 33 264 small molecules for their ability to inhibit the adhesion of washed platelets to immobilized fibrinogen at 16 μM. A total of 102 compounds demonstrated 50% or more inhibition, and one of these (compound 1, 265 g/mol) inhibited ADP-induced platelet aggregation (IC50: 13± 5 μM), the binding of soluble fibrinogen to platelets induced by mAb AP5, and the binding of soluble fibrinogen and a cyclic RGD peptide to purified αIIbβ3. Compound 1 did not affect the function of GPIb, α2β1, or the other β3 family receptor αVβ3. Molecular docking simulations suggest that compound 1 interacts with αIIb but not β3. Compound 1 induced partial exposure of an αIIb ligand-induced binding site (LIBS), but did not induce exposure of 2 β3 LIBS. Transient exposure of purified αIIbβ3 to eptifibatide, but not compound 1, enhanced fibrinogen binding (“priming”). Compound 1 provides a prototype for small molecule selective inhibition of αIIbβ3, without receptor priming, via targeting αIIb.

scholarly journals A Simple Displacement Aptamer Assay on Resistive Pulse Sensor for Small Molecule Detection

2020 ◽  
Author(s):  
Rhushabh Maugi ◽  
bernadette gamble ◽  
david bunka ◽  
Mark Platt
Keyword(s):  
Small Molecules ◽  
Small Molecule ◽  
Label Free ◽  
Resistive Pulse ◽  
Pulse Sensor ◽  
Label Free Detection ◽  
Ssdna Aptamer ◽  
Aptamer Assay ◽  
Small Molecule Detection ◽  
Surface Changes

A universal aptamer-based sensing strategy is proposed using DNA modified nanocarriers and Resistive Pulse Sensing for the rapid and label free detection of small molecules. The surface of a magnetic nanocarrier was first modified with a ssDNA aka linker which is designed to be partially complimentary in sequence to a ssDNA aptamer. The aptamer and linker form a stable dsDNA complex on the nanocarriers surface. Upon the addition of the target molecule, a conformational change takes place where the aptamer preferentially binds to the target over the linker; causing the aptamer to be released into solution. The RPS measures the change in velocity of the nanocarrier as its surface changes from dsDNA to ssDNA, and its velocity is used as a proxy for the concentration of the target. We illustrate the versatility of the assay by demonstrating the detection of the antibiotic Moxifloxacin, and chemotherapeutics Imatinib and Irinotecan.

scholarly journals Integrative x-ray structure and molecular modeling for the rationalization of procaspase-8 inhibitor potency and selectivity

2019 ◽  
Author(s):  
Janice H. Xu ◽  
Jerome Eberhardt ◽  
Brianna Hill-Payne ◽  
Gonzalo E. González-Páez ◽  
José Omar Castellón ◽  
...  
Keyword(s):  
Molecular Modeling ◽  
Small Molecules ◽  
Small Molecule ◽  
Conformational Changes ◽  
Active Sites ◽  
Structural Similarity ◽  
X Ray ◽  
X Ray Crystallography ◽  
Molecule Inhibitor ◽  
High Structural Similarity

AbstractCaspases are a critical class of proteases involved in regulating programmed cell death and other biological processes. Selective inhibitors of individual caspases, however, are lacking, due in large part to the high structural similarity found in the active sites of these enzymes. We recently discovered a small-molecule inhibitor, 63-R, that covalently binds the zymogen, or inactive precursor (pro-form), of caspase-8, but not other caspases, pointing to an untapped potential of procaspases as targets for chemical probes. Realizing this goal would benefit from a structural understanding of how small molecules bind to and inhibit caspase zymogens. There have, however, been very few reported procaspase structures. Here, we employ x-ray crystallography to elucidate a procaspase-8 crystal structure in complex with 63-R, which reveals large conformational changes in active-site loops that accommodate the intramolecular cleavage events required for protease activation. Combining these structural insights with molecular modeling and mutagenesis-based biochemical assays, we elucidate key interactions required for 63-R inhibition of procaspase-8. Our findings inform the mechanism of caspase activation and its disruption by small molecules, and, more generally, have implications for the development of small molecule inhibitors and/or activators that target alternative (e.g., inactive precursor) protein states to ultimately expand the druggable proteome.

scholarly journals STEM-20. A CANCER STEM CELL-SELECTIVE APOPTOSIS-INDUCING SMALL MOLECULE FOR THE TREATMENT OF GBM

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii200-ii200
Author(s):  
Stephen Skirboll ◽  
Natasha Lucki ◽  
Genaro Villa ◽  
Naja Vergani ◽  
Michael Bollong ◽  
...  
Keyword(s):  
Stem Cells ◽  
Cancer Stem Cells ◽  
Small Molecules ◽  
Small Molecule ◽  
Large Scale ◽  
Critical Role ◽  
Tumor Formation ◽  
Cell Type ◽  
Caspase 1 ◽  
Activation Assay

Abstract INTRODUCTION Glioblastoma multiforme (GBM) is the most aggressive form of primary brain cancer. A subpopulation of multipotent cells termed GBM cancer stem cells (CSCs) play a critical role in tumor initiation and maintenance, drug resistance, and recurrence following surgery. New therapeutic strategies for the treatment of GBM have recently focused on targeting CSCs. Here we have used an unbiased large-scale screening approach to identify drug-like small molecules that induce apoptosis in GBM CSCs in a cell type-selective manner. METHODS A luciferase-based survival assay of patient-derived GBM CSC lines was established to perform a large-scale screen of ∼one million drug-like small molecules with the goal of identifying novel compounds that are selectively toxic to chemoresistant GBM CSCs. Compounds found to kill GBM CSC lines as compared to control cell types were further characterized. A caspase activation assay was used to evaluate the mechanism of induced cell death. A xenograft animal model using patient-derived GBM CSCs was employed to test the leading candidate for suppression of in vivo tumor formation. RESULTS We identified a small molecule, termed RIPGBM, from the cell-based chemical screen that induces apoptosis in primary patient-derived GBM CSC cultures. The cell type-dependent selectivity of RIPGBM appears to arise at least in part from redox-dependent formation of a proapoptotic derivative, termed cRIPGBM, in GBM CSCs. cRIPGBM induces caspase 1-dependent apoptosis by binding to receptor-interacting protein kinase 2 (RIPK2) and acting as a molecular switch, which reduces the formation of a prosurvival RIPK2/TAK1 complex and increases the formation of a proapoptotic RIPK2/caspase 1 complex. In an intracranial GBM xenograft mouse model, RIPGBM was found to significantly suppress tumor formation. CONCLUSIONS Our chemical genetics-based approach has identified a small molecule drug candidate and a potential drug target that selectively targets cancer stem cells and provides an approach for the treatment of GBMs.

scholarly journals Advances in emergent biological recognition elements and bioelectronics for diagnosing COVID-19

2021 ◽  
Vol 4 (1) ◽  
pp. 231-247
Author(s):  
Praopim Limsakul ◽  
Krit Charupanit ◽  
Chochanon Moonla ◽  
Itthipon Jeerapan
Keyword(s):  
Biological Recognition ◽  
Recognition Elements

scholarly journals RE-SELEX: Restriction Enzyme-Based Evolution of Structure-Switching Aptamer Biosensors 

2021 ◽  
Author(s):  
Aimee Alice Sanford ◽  
Alexandra E Rangel ◽  
Trevor A Feagin ◽  
Robert G Lowery ◽  
Hector S Argueta-Gonzalez ◽  
...  
Keyword(s):  
Small Molecule ◽  
Restriction Enzyme ◽  
High Affinity ◽  
Recognition Elements ◽  
Evolution Of Structure ◽  
Structure Switching

Aptamers are widely employed as recognition elements in small molecule biosensors due to their ability to recognize small molecule targets with high affinity and selectivity. Structure-switching aptamers are particularly promising...

Sign in / Sign up

Export Citation Format

Share Document