Track topics on Twitter Track topics that are important to you
Allostery is generally considered as a thermodynamic equilibrium phenomenon. In contrast to this, we show here that this mechanism offers a key strategy to rationally design out-of-equilibrium synthetic devices. We demonstrate this by engineering allosteric DNA-based nanodevices for the transient load and release of small organic molecules. To demonstrate the versatility and generality of our approach we have employed two model DNA-based aptamers that bind ATP and cocaine through a target-induced conformational change. We have rationally re-engineered these aptamers so that their affinity towards their specific target is controlled by a DNA sequence acting as an allosteric inhibitor. The use of an enzyme that specifically cleaves the inhibitor only when it is bound to the aptamer generates a transient allosteric control that leads to the temporal release of ATP or cocaine from the aptamers. Our approach confirms how the programmability and predictability of nucleic acids make synthetic DNA/RNA the perfect candidate material to re-engineer synthetic receptors that can undergo chemical fuel-triggered release of different kinds of small molecule cargoes (ATP and cocaine) and to rationally design non-equilibrium systems. Moreover, our study illustrates the potential of transient allosteric regulation as a tool to control the functions of synthetic dissipative devices.
This article was published in the following journal.
Name: Angewandte Chemie (International ed. in English)
Allosteric modulators bound to structurally diverse allosteric sites can achieve better pharmacological advantages than orthosteric ligands. The discovery of allosteric modulators, however, has been t...
Various thermo-responsive polymers have been developed for controlled drug delivery upon the local application of external heat. The development of thermo-responsive polymers of high biocompatibility ...
Artificial stimuli-responsive hydrogels that can mimic natural extracellular matrix for growth and release of cancer spheroids (CSs) have attracted much attention. However, such hydrogels still face a...
Nanoparticles based on biodegradable polymers are well-known as approved carrier systems for a diversity of drugs. Despite their advantages, such as the option of an active drug targeting or the physi...
Aptamers that recognize specific cells in a complex environment have emerged as invaluable molecular tools in bioanalysis and in the development of targeted therapeutics. The selective recognition of ...
Cocaine dependence is a major public health problem; an effective primary treatment for cocaine dependent individuals has yet to be found. The purpose of this study is to identify subpopu...
Cocaine is one of the most widely abused drugs in the United States. Memantine is a type of drug called an NMDA receptor antagonist. It works by decreasing normal excitement in the brain...
Cocaine abuse continues to represent a significant public-health concern. Cocaine likely creates its addictive effects by increasing levels of dopamine, a chemical found in the brain. GABA...
The purpose of this study is to evaluate the effects of buprenorpine on cocaine taking and on the physiological and subjective effects of cocaine, including cocaine craving in non-opiate d...
The purpose of this study is to determine whether maintenance on different oral doses of sustained release d-amphetamine (SR-AMP) combined with constant-dose sublingual buprenorphine (BUP)...
The purified, alkaloidal, extra-potent form of cocaine. It is smoked (free-based), injected intravenously, and orally ingested. Use of crack results in alterations in function of the cardiovascular system, the autonomic nervous system, the central nervous system, and the gastrointestinal system. The slang term "crack" was derived from the crackling sound made upon igniting of this form of cocaine for smoking.
A method of generating a large library of randomized nucleotides and selecting NUCLEOTIDE APTAMERS by iterative rounds of in vitro selection. A modified procedure substitutes AMINO ACIDS in place of NUCLEOTIDES to make PEPTIDE APTAMERS.
SMOKING of COCAINE.
Disorders related or resulting from use of cocaine.
An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake.
Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...
Enzymes are proteins that catalyze (i.e., increase the rates of) chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical re...