A clear difference in the enthalpy changes derived from spectroscopic and calorimetric measurements has recently been shown. The exact interpretation of this deviation varied from study to study, but it was generally attributed to the non-two-state transition and heat capacity change. Although the temperature-dependent thermodynamics of the duplex formation was often implied, systemic and extensive studies have been lacking in universally assigning the appropriate thermodynamic parameter sets. In the present study, the 24 DNA/DNA and 41 RNA/DNA oligonucleotide duplexes, designed to avoid the formation of hairpin or slipped duplex structures and to limit the base pair length less than 12 bp, were selected to evaluate the heat capacity changes and temperature-dependent thermodynamic properties of duplex formation. Direct comparison reveals that the temperature-independent thermodynamic parameters could provide a reasonable approximation only when the temperature of interest has a small deviation from the mean melting temperature over the experimental range. The heat capacity changes depend on the base composition and sequences and are generally limited in the range of )160 to % )40 calAEmol )1 AEK )1 per base pair. In contrast to the enthalpy and entropy changes, the free energy change and melting temperature are relatively insensitive to the heat capacity change. Finally, the 16 NN-model free energy parameters and one helix initiation at physiological temperature were extracted from the temperature-dependent thermodynamic data of the 41 RNA/DNA hybrids.Keywords: heat capacity change; temperature-dependent thermodynamics; enthalpy-entropy compensation; the NN-model parameters.With the dramatic progress in the human genome project, many gene sequences are well known but their structure and function are not yet clearly understood, and therefore, thermodynamic optimization strategy plays more and more important role in understanding and predicting the sequence-dependent higher-ordered structures of nucleic acids [1][2][3][4]. Knowledge of the thermodynamics of nucleic acids will also be very useful for designing appropriate screening or scanning experiments for identifying the genetic markers for diseases [5], sequencing single nucleotide polymorphisms on a genome-wide scale [6], calculating hybridization equilibria for purposes of designing the PCR and rolling-cycle amplification [7,8], selecting optimal conditions for hybridization experiments, and determining the minimum length of a probe required for the hybridization and cloning experiments [9,10]. Moreover, the development of DNA chips for rapidly screening and sequencing unknown DNAs mainly relies on the ability to predict the thermodynamic stability of the complexes formed by the oligonucleotide probes [11,12].Spectroscopic and calorimetric measurements are two widely applied methods to determine the thermodynamic parameters of nucleic acids [13][14][15]. The UV measurement is highly sensitive and only small sample units are required for a full set of measure...

The effects of cytosine protonation and various cations on the properties of parallel pyrimidine motif DNA triplexes were intensively investigated and characterized by several different techniques, such as circular dichroism (CD) conformation, ultraviolet (UV) melting, differential scanning calorimetry (DSC) thermal denaturation, and surface plasmon resonance (SPR) real-time dynamics. The comparative CD spectra of the triplex and the corresponding homoduplexes showed that the negative peak at approximately 218 nm would be the eigenpeak of the Hoogsteen paired strand, and moreover, the formation pathway of a triplex was significantly pH-dependent and fell into three groups: under acidic conditions, the triplex is formed by a one-step docking, under near physiological conditions, the Watson-Crick duplex is first structured and then accepts the Hoogsteen third strand into its major groove, and under basic conditions, the triplex is not formed. The pH-dependent thermodynamics of the global triplex, the Watson-Crick antiparallel duplex, and the Crick-Hoogsteen parallel duplex were comparatively discussed for the first time. These data revealed that the thermodynamic stabilities of the Watson-Crick-Hoogsteen triplex and the Crick-Hoogsteen duplex would be strongly dependent on cytosine protonation, but a low-pH environment somewhat destabilized the Watson-Crick duplex. The binding energy of triplex formation would be different from the unfolding energy of triplex melting under acidic conditions due to the disparity in the pathway between the formation and unfolding of a triplex. Real-time dynamic measurements showed that the association and dissociation rate constants of a duplex-to-triplex formation are (1.98 +/- 0.24) x 10(3) M(-1) s(-1) and (4.09 +/- 0.96) x 10(-4) s(-1) at 20 degrees C and pH 6.0, respectively. The formation energy of the duplex-to-triplex transition derived from SPR measurements was in agreement with the unfolding energy of the free Hoogsteen paired duplex derived from UV measurements. The calorimetric enthalpies of the triplex-to-duplex-to-single transition were 39.3 and 75.3 kcal/mol under near physiological conditions (pH 7.0), respectively, which were underestimated relative to the van't Hoff enthalpies. In addition, the effects of various cations, ionic strength, mixed-valent cations, and the position of the C(+)xG.C triplets on the thermodynamics of the triplexes were addressed under near physiological conditions. The interaction of metal ions with the triplexes clearly depended on the type and ionic strength of the cations, and the efficiency with which the cations stabilized the global triplex was in the order Mg(2+) > Mn(2+) > Ca(2+) > Ba(2+) >> Na(+). These observations would be useful for the design of triplex-forming oligonucleotides for antigene drugs and therapeutic purposes.

Structural characteristics and thermodynamic properties of dG 3 (T 2 AG 3 ) 3 , d(C 3 TA 2 ) 3 C 3 and dG 3 (T 2 AG 3 ) 3 / d(C 3 TA 2 ) 3 C 3 were intensively investigated. It was indicated that metal ions greatly a¡ected the conformation and stability of the G-quadruplex. A competition of a structure transition among the G-quadruplex, I-motif, and the duplex was con¢rmed to be dependent on both cation species and pH values. The structural competitive mechanism is discussed for the ¢rst time. This study shows an intriguing potential in modulating DNA structures in vivo, which is of great importance in drug design and cancer chemotherapy. ß

Cell membrane coating has recently emerged as a promising biomimetic approach to engineering nanoparticles (NPs) for targeted drug delivery. However, simple cell membrane coating may not meet the need for efficient drug delivery to the brain. Here, a novel molecular engineering strategy to modify the surface of NPs with a cell membrane coating for enhanced brain penetration is reported. By using poly(lactic‐co‐glycolic) acid NPs as a model, it is shown that delivery of NPs to the ischemic brain is enhanced through surface coating with the membrane of neural stem cells (NSCs), and the delivery efficiency can be further increased using membrane isolated from NSCs engineered for overexpression of CXCR4. It is found that this enhancement is mediated by the chemotactic interaction of CXCR4 with SDF‐1, which is enriched in the ischemic microenvironment. It is demonstrated that the resulting CXCR4‐overexpressing membrane‐coated NPs, termed CMNPs, significantly augment the efficacy of glyburide, an anti‐edema agent, for stroke treatment. The study suggests a new approach to improving drug delivery to the ischemic brain and establishes a novel formulation of glyburide that can be potentially translated into clinical applications to improve management of human patients with stroke.

A mesoporous silica nanoparticle system with a lactose-mediated targeting effect was demonstrated to deliver a platinum(iv) prodrug for liver cancer therapy.