528 research outputs found
Robustness and modularity properties of a non-covalent DNA catalytic reaction
The biophysics of nucleic acid hybridization and strand displacement have been used for the rational design of a number of nanoscale structures and functions. Recently, molecular amplification methods have been developed in the form of non-covalent DNA catalytic reactions, in which single-stranded DNA (ssDNA) molecules catalyze the release of ssDNA product molecules from multi-stranded complexes. Here, we characterize the robustness and specificity of one such strand displacement-based catalytic reaction. We show that the designed reaction is simultaneously sensitive to sequence mutations in the catalyst and robust to a variety of impurities and molecular noise. These properties facilitate the incorporation of strand displacement-based DNA components in synthetic chemical and biological reaction networks
Affinity chromatography in dynamic combinatorial libraries: one-pot amplification and isolation of a strongly binding receptor
We report the one-pot amplification and isolation of a nanomolar receptor in a multibuilding block aqueous dynamic combinatorial library using a polymer-bound template. By appropriate choice of a poly(N,N-dimethylacrylamide)-based support, unselective ion-exchange type behaviour between the oppositely charged cationic guest and polyanionic hosts was overcome, such that the selective molecular recognition arising in aqueous solution reactions is manifest also in the analogous templated solid phase DCL syntheses. The ability of a polymer bound template to identify and isolate a synthetic receptor via dynamic combinatorial chemistry was not compromised by the large size of the library, consisting of well over 140 theoretical members, demonstrating the practical advantages of a polymer-supported DCL methodology
Structure of DNA-Functionalized Dendrimer Nanoparticles
Atomistic molecular dynamics simulations have been carried out to reveal the
characteristic features of ethylenediamine (EDA) cored protonated poly amido
amine (PAMAM) dendrimers of generation 3 (G3) and 4 (G4) that are
functionalized with single stranded DNAs (ssDNAs). The four ssDNA strands that
are attached via alkythiolate [-S (CH2)6-] linker molecule to the free amine
groups on the surface of the PAMAM dendrimers observed to undergo a rapid
conformational change during the 25 ns long simulation period. From the RMSD
values of ssDNAs, we find relative stability in the case of purine rich ssDNA
strands than pyrimidine rich ssDNA strands. The degree of wrapping of ssDNA
strands on the dendrimer molecule was found to be influenced by the charge
ratio of DNA and the dendrimer. As G4 dendrimer contains relatively more
positive charge than G3 dendrimer, we observe extensive wrapping of ssDNAs on
the G4 dendrimer. The ssDNA strands along with the linkers are seen to
penetrate the surface of the dendrimer molecule and approach closer to the
center of the dendrimer indicating the soft sphere nature of the dendrimer
molecule. The effective radius of DNA-functionalized dendrimer nanoparticle was
found to be independent of base composition of ssDNAs and was observed to be
around 19.5 {\AA} and 22.4 {\AA} when we used G3 and G4 PAMAM dendrimer as the
core of the nanoparticle respectively. The observed effective radius of
DNA-functionalized dendrimer molecule apparently indicates the significant
shrinkage in the structure that has taken place in dendrimer, linker and DNA
strands. As a whole our results describe the characteristic features of
DNA-functionalized dendrimer nanoparticle and can be used as strong inputs to
design effectively the DNA-dendrimer nanoparticle self-assembly for their
active biological applications.Comment: 13 pages, 10 figures, 3 Table
Tetramolecular G-quadruplex formation pathways studied by electrospray mass spectrometry
Electrospray mass spectrometry was used to investigate the mechanism of tetramolecular G-quadruplex formation by the DNA oligonucleotide dTG5T, in ammonium acetate. The intermediates and products were separated according to their mass (number of strands and inner cations) and quantified. The study of the temporal evolution of each species allows us to propose the following formation mechanism. (i) Monomers, dimers and trimers are present at equilibrium already in the absence of ammonium acetate. (ii) The addition of cations promotes the formation of tetramers and pentamers that incorporate ammonium ions and therefore presumably have stacked guanine quartets in their structure. (iii) The pentamers eventually disappear and tetramers become predominant. However, these tetramers do not have their four strands perfectly aligned to give five G-quartets: the structures contain one ammonium ion too few, and ion mobility spectrometry shows that their conformation is more extended. (iv) At 4°C, the rearrangement of the kinetically trapped tetramers with presumably slipped strand(s) into the perfect G-quadruplex structure is extremely slow (not complete after 4 months). We also show that the addition of methanol to the monomer solution significantly accelerates the cation-induced G-quadruplex assembly
Functionalization and Self-Assembly of DNA Bidimensional Arrays
Oligonucleotides carrying amino, thiol groups, as well as fluorescein, c-myc peptide sequence and nanogold at internal positions were prepared and used for the assembly of bidimensional DNA arrays
Programmable Periodicity of Quantum Dot Arrays with DNA Origami Nanotubes
To fabricate quantum dot arrays with programmable periodicity, functionalized DNA origami nanotubes were developed. Selected DNA staple strands were biotin-labeled to form periodic binding sites for streptavidin-conjugated quantum dots. Successful formation of arrays with periods of 43 and 71 nm demonstrates precise, programmable, large-scale nanoparticle patterning; however, limitations in array periodicity were also observed. Statistical analysis of AFM images revealed evidence for steric hindrance or site bridging that limited the minimum array periodicity
Reprogramming the assembly of unmodified DNA with a small molecule
The ability of DNA to store and encode information arises from base pairing of the four-letter nucleobase code to form a double helix. Expanding this DNA ‘alphabet’ by synthetic incorporation of new bases can introduce new functionalities and enable the formation of novel nucleic acid structures. However, reprogramming the self-assembly of existing nucleobases presents an alternative route to expand the structural space and functionality of nucleic acids. Here we report the discovery that a small molecule, cyanuric acid, with three thymine-like faces reprogrammes the assembly of unmodified poly(adenine) (poly(A)) into stable, long and abundant fibres with a unique internal structure. Poly(A) DNA, RNA and peptide nucleic acid all form these assemblies. Our studies are consistent with the association of adenine and cyanuric acid units into a hexameric rosette, which brings together poly(A) triplexes with a subsequent cooperative polymerization. Fundamentally, this study shows that small hydrogen-bonding molecules can be used to induce the assembly of nucleic acids in water, which leads to new structures from inexpensive and readily available materials
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