Thermodynamics in folding transition of DNA

Recently, it has been found that individual giant DNA molecules exhibit a discrete transition, or first order phase‐transition, between the compact folded state and the elongated coiled state, i.e., the folding transition. In order to clarify the thermodynamics in the folding transition of single DNA molecules, we have studied the temperature effect on the bimodal distribution of conformation for the ensemble of T4DNA chains (166 kbps) in both poly(ethylene glycol) (PEG) and spermidine (SPD), using single‐chain observation with fluorescence microscopy. From the van't Hoff relationship, the entropy change in the transition from the compact state to the unfolded state is deduced as, ΔS = +11, +38 k/molecule in the aqueous solution of PEG with sodium chloride and potassium chloride, respectively, where k is Boltzmann's constant, whereas, ΔS with SPD is estimated to be −32 k/molecule. The values of ΔS with the transition are discussed in term of the translational entropy of counterions together with the hydration effect.     

Metal-induced chiral folding of depsipeptide dendrimers

The synthesis and metal complexation of chiral depsipeptide dendrimers 3 and 7 containing an ethylenediaminetetraacetic acid (EDTA) ester-derived core is reported. The EDTA ester cavity of these dendrimers selectively complexes Zn(2+) and Cu(2+) ions leading to diastereoselective folding. To elucidate the coordination motif in the resulting "foldamers" of 3-ZnCl(2), 7-ZnCl(2), 3-CuCl(2), and 7-CuCl(2), the coordination behavior of the tetramethyl ester of EDTA (8) has been investigated as a model case. The corresponding complexes 8-ZnCl(2) and 8-CuCl(2) have been structurally characterized by (1)H NMR spectroscopy and X-ray analysis. The complexes involve the inherently chiral octahedral cis-alpha coordination motif, in which 8 serves as a tetradentate ligand. In the case of the Zn(II) complex 8-ZnCl(2), both Deltacis-alpha(S,S,lambda) and Lambdacis-alpha(R,R,lambda) stereoisomers were found in the unit cell. For the Cu(II) complex 8-CuCl(2), only one stereoisomer, namely Deltacis-alpha(S,S,lambda) was found in the crystal under investigation. (1)H NMR spectroscopy has shown that the same coordination motif is diastereoselectively formed in the chiral Zn(2+) dendrimers 3-ZnCl(2) and 7-ZnCl(2). Likewise, the calculated CD spectrum of the Deltacis-alpha(S,S,lambda) stereoisomer of the model complex 8-CuCl(2) shows good agreement with the experimental spectrum of the Cu(II) dendrimers 3-CuCl(2) and 7-CuCl(2), allowing assignment of the absolute configurations of the preferred foldamers as Lambdacis-alpha(R,R,lambda) for 3-CuCl(2) and Deltacis-alpha(S,S,lambda) for 7-CuCl(2). This work represents the first example of metal-complexation-mediated diastereoselective folding of chiral dendrimers with known absolute configuration.     

Biased helical folding of chiral oligoindole foldamers

Oligoindole-based chiral foldamers have been synthesized by incorporating (S)- or (R)-1-phenylethylamine to both ends of the tetraindole scaffold. The oligoindoles fold into a helical conformation upon binding an anion by hydrogen bonds, which gives rise to an induced circular dichroism (CD) signal of large amplitude, implying the preferential formation of one helical isomer over another. Theoretical calculations suggest that the (P)-helix of the (S,S)-oligoindole 8a be more energetically stable than the corresponding (M)-helix.     

DNA origami: the art of folding DNA

The advent of DNA origami technology greatly simplified the design and construction of nanometer-sized DNA objects. The self-assembly of a DNA-origami structure is a straightforward process in which a long single-stranded scaffold (often from the phage M13mp18) is folded into basically any desired shape with the help of a multitude of short helper strands. This approach enables the ready generation of objects with an addressable surface area of a few thousand nm(2) and with a single "pixel" resolution of about 6 nm. The process is rapid, puts low demands on experimental conditions, and delivers target products in high yields. These features make DNA origami the method of choice in structural DNA nanotechnology when two- and three-dimensional objects are desired. This Minireview summarizes recent advances in the design of DNA origami nanostructures, which open the door to numerous exciting applications.     

Nanoscale dewetting transition in protein complex folding

In a previous study, a surprising drying transition was observed to take place inside the nanoscale hydrophobic channel in the tetramer of the protein melittin. The goal of this paper is to determine if there are other protein complexes capable of displaying a dewetting transition during their final stage of folding. We searched the entire protein data bank (PDB) for all possible candidates, including protein tetramers, dimers, and two-domain proteins, and then performed the molecular dynamics (MD) simulations on the top candidates identified by a simple hydrophobic scoring function based on aligned hydrophobic surface areas. Our large scale MD simulations found several more proteins, including three tetramers, six dimers, and two two-domain proteins, which display a nanoscale dewetting transition in their final stage of folding. Even though the scoring function alone is not sufficient (i.e., a high score is necessary but not sufficient) in identifying the dewetting candidates, it does provide useful insights into the features of complex interfaces needed for dewetting. All top candidates have two features in common: (1) large aligned (matched) hydrophobic areas between two corresponding surfaces, and (2) large connected hydrophobic areas on the same surface. We have also studied the effect on dewetting of different water models and different treatments of the long-range electrostatic interactions (cutoff vs PME), and found the dewetting phenomena is fairly robust. This work presents a few proteins other than melittin tetramer for further experimental studies of the role of dewetting in the end stages of protein folding.     

Self-assembly of chiral DNA nanotubes

A system of DNA "tiles" that is designed to assemble to form two-dimensional arrays is observed to form narrow ribbons several micrometers in length. The uniform width of the ribbons and lack of frayed edges lead us to propose that they are arrays that have curled and closed on themselves to form tubes. This proposal is confirmed by the observation of tubes with helical order.     

pH-induced intramolecular folding dynamics of i-motif DNA

Using the combination of fluorescence resonance energy transfer (FRET) and fluorescence correlation spectroscopy (FCS) technique, we investigate the mechanism and dynamics of the pH-induced conformational change of i-motif DNA in the bulk phases and at the single-molecule level. Despite numerous studies on i-motif that is formed from cytosine (C)-rich strand at slightly acidic pH, its detailed conformational dynamics have been rarely reported. Using the FRET technique to provide valuable information on the structure of biomolecules such as a protein and DNA, we clearly show that the partially folded species as well as the single-stranded structure coexist at neutral pH, supporting that the partially folded species may exist substantially in vivo and play an important role in a process of gene expression. By measuring the FCS curves of i-motif, we observed the gradual decrease of the diffusion coefficient of i-motif with increasing pH. The quantitative analysis of FCS curves supports that the gradual decrease of diffusion coefficient (D) associated with the conformational change of i-motif is not only due to the change in the intermolecular interaction between i-motif and solvent accompanied by the increase of pH but also due to the change of the shape of DNA. Furthermore, FCS analysis showed that the intrachain contact formation and dissociation for i-motif are 5-10 times faster than that for the open form. The fast dynamics of i-motif with a compact tetraplex is due to the intrinsic conformational changes at the fluorescent site including the motion of alkyl chain connecting the dye to DNA, whereas the slow intrachain contact formation observed from the open form is due to the DNA motion corresponding to an early stage interaction in the folding process of the unstructured open form.     

Thermodynamics of the DNA helix-coil transition

The thermodynamics of the DNA helix-coil transition is studied, starting from the thermodynamical potential difference between the states helix and coil; this potential difference is understood as the difference in free energies. With only three parameters obtained from experimental data different quantities of the T₂ phage DNA molecule are calculated. It is observed that the phase transition is of second order.     

Asymmetric patterning drives the folding of a tripodal DNA nanotweezer

DNA tweezers have emerged as powerful devices for a wide range of biochemical and sensing applications; however, most DNA tweezers consist of single units activated by DNA recognition, limiting their range of motion and ability to respond to complex stimuli. Herein, we present an extended, tripodal DNA nanotweezer with a small molecule junction. Simultaneous, asymmetric elongation of our molecular core is achieved using polymerase chain reaction (PCR) to produce length- and sequence-specific DNA arms with repeating DNA regions. When rigidified, our DNA tweezer can be addressed with streptavidin-binding ligands. Full control over the number, separation, and location of these ligands enables site-specific streptavidin recognition; all three arms of the DNA nanotweezer wrap around multiple streptavidin units simultaneously. Our approach combines the simplicity of DNA tile arrays with the size regime normally provided by DNA origami, offering an integrated platform for the use of branched DNA scaffolds as structural building blocks, protein sensors, and dynamic, stimuli-responsive materials.

An extended, multivalent DNA nanotweezer that undergoes large-scale molecular motion upon protein recognition is presented. Our method based on “printing-elongation-folding” combines the DNA-minimal aspect of DNA tile-based assembly, with complexity of DNA origami.     

Degeneracy of rotational viscosities at the chiral smectic C-smectic A transition in DOBAMBC

From measurements of the electroclinic effect and the dielectric strength of the soft mode close to the chiral smectic C-smectic A transition we show that the rotational viscosities associated with the Goldstone and soft modes are degenerate at T_c, in agreement with the predictions of the theoretical model.     

Photophysics and redox behavior of chiral transition metal polymers

The absorption and emission spectra, excited-state lifetimes, quantum yields, and electrochemical measurements have been obtained for a new series of chiral complexes based on three different chiral 2,2':6',2' '-terpyridine ligands, (-)-ctpy, (-)-[ctpy-x-ctpy], and (-)-[ctpy-b-ctpy], with one, two, or multiple Ru metal centers. The room-temperature absorption and emission maxima of [[((-)-ctpy)Ru]-(-)-[ctpy-b-ctpy]-[Ru((-)-ctpy)]](PF(6))(4) and ((-)-[ctpy-b-ctpy])-[[Ru((-)-[ctpy-b-ctpy])](PF(6))(2)](n) were shifted to lower energies and also exhibited significantly longer luminescence lifetimes when compared to [Ru((-)-ctpy)(2)](PF(6))(2), [[((-)-ctpy)Ru]-(-)-[ctpy-x-ctpy]-[Ru((-)-ctpy)]](PF(6))(4), and ((-)-[ctpy-x-ctpy])-[[Ru((-)-[ctpy-x-ctpy])](PF(6))(2)](n). In terms of their electrochemical behavior, all of the complexes studied exhibited one Ru-centered and two ligand-centered redox waves and the [[((-)-ctpy)Ru]-(-)-[ctpy-x-ctpy]-[Ru((-)-ctpy)]](PF(6))(4), ((-)-[ctpy-x-ctpy])-[[Ru((-)-[ctpy-x-ctpy])](PF(6))(2)](n), and ((-)-[ctpy-b-ctpy])-[[Ru((-)-[ctpy-b-ctpy])](PF(6))(2)](n)() complexes were found to electrodeposit upon ligand-based reduction. The difference between the formal potentials of the Ru-centered and the first ligand-centered (least negative) waves corresponded linearly with the changes in the observed emission energies. The shifts in energy are discussed using a particle-in-a-box model, and the luminescence lifetimes are discussed in terms of the structure of the excited-state manifold.     

An unnatural amino acid that induces beta-sheet folding and interaction in peptides

This paper introduces a unique amino acid that can readily be incorporated into peptides to make them fold into beta-sheetlike structures that dimerize through beta-sheet interactions. This new amino acid, Orn(i-PrCO-Hao), consists of an ornithine residue with the beta-strand-mimicking amino acid Hao [J. Am. Chem. Soc. 2000, 122, 7654-7661] attached to its side chain. When Orn(i-PrCO-Hao) is incorporated into a peptide, or appended to its N-terminus, the Hao group hydrogen bonds to the three subsequent residues to form a beta-sheetlike structure. The amino acid Orn(i-PrCO-Hao) is readily used in peptide synthesis as its Fmoc derivative, Fmoc-Orn(i-PrCO-Hao)-OH (3). Fmoc-Orn(i-PrCO-Hao)-OH behaves like a regular amino acid in peptide synthesis and was uneventfully incorporated into the peptide o-anisoyl-Val-Orn(i-PrCO-Hao)-Phe-Ile-Leu-NHMe (4) through standard automated Fmoc solid-phase peptide synthesis, with DIC and HOAt as the coupling agent for Fmoc-Orn(i-PrCO-Hao)-OH and o-anisic acid and HATU as the coupling agent for all other couplings. A second synthetic strategy was developed to facilitate the preparation of peptides with N-terminal Orn(i-PrCO-Hao) residues, which avoids the need for the preparation of Fmoc-Orn(i-PrCO-Hao)-OH. In this strategy, Boc-Orn(Fmoc)-OH is used as the penultimate amino acid in the peptide synthesis, and i-PrCO-Hao-OH (2) is used as the final amino acid. N-Terminal Orn(i-PrCO-Hao) peptide H-Orn(i-PrCO-Hao)-Phe-Ile-Leu-NHMe.TFA (5) was prepared in a fashion similar to that for 4, using DIC and HOAt as the coupling agent for i-PrCO-Hao-OH and HATU as the coupling agent for all other couplings. 1H NMR transverse-ROESY, coupling constant, and chemical shift studies establish that peptide 4 forms a dimeric beta-sheetlike structure in CDCl3 solution. The 1H NMR studies also suggest that the ornithine unit adopts a well-defined turn conformation. Analogous 1H NMR studies of peptide 5 indicate that this TFA salt folds but does not dimerize in CD3OD solution. Collectively, these synthetic and spectroscopic studies establish that the amino acid Orn(i-PrCO-Hao) induces beta-sheet structure and interactions in peptides in suitable organic solvents. Unlike the Hao amino acid, which acts as a prosthetic to replace three residues of the peptide strand, the Orn(i-PrCO-Hao) amino acid acts as a splint that helps enforce a beta-sheetlike structure without replacing the residues and their side chains. This feature of Orn(i-PrCO-Hao) is important, because it allows the creation of beta-sheet structure with minimal perturbation of the peptide sequence.     

Facile synthesis of a chiral polymeric helix; folding by intramolecular hydrogen bonding

In a single condensation step, a poly-ureidophthalimide is synthesized, which folds into a chiral, helical architecture according to circular dichroism spectroscopy.     

Paramagnetic chiral mesophases of Shiff's base complexes of transition metals

Copper(II), nickel(II) and oxovanadium(IV) complexes of 4-(4-heptyloxybenzoyloxy)-N-(S)-2-methylbutylsalicylaldimine, as well as the parent ligand, were studied by optical and DSC methods. For the first two complexes, there exist between a tightly twisted chiral nematic phase and the isotropic liquid either some blue phases or novel-type amorphous phases, with their temperature ranges depending significantly on the metal centre. For the third complex, direct isotropization takes place.