Heteromeric guanosine (G)-quadruplex derived antenna modules with directional energy transfer.

A heteromeric guanosine (G)-quadruplex centered self-assembly approach is developed to prepare compact light-harvesting antenna modules featuring multiple donor dyes and a single toehold region. Due to the mix-and-match nature of our approach, the number and placement of donor dyes can be readily fine-tuned via quadruplex assembly. Moreover, hybridization of the toehold with an acceptor containing sequence results in directional energy transfer ensembles with effective absorption coefficients in the 105 M-1 cm-1 range. These compact antennas exhibit system efficiencies that are comparable to much larger and elaborate DNA architectures containing numerous DNA strands.

DNA Strand Displacement Driven by Host-Guest Interactions.

Base-pair-driven toehold-mediated strand displacement (BP-TMSD) is a fundamental concept employed for constructing DNA machines and networks with a gamut of applications─from theranostics to computational devices. To broaden the toolbox of dynamic DNA chemistry, herein, we introduce a synthetic surrogate termed host-guest-driven toehold-mediated strand displacement (HG-TMSD) that utilizes bioorthogonal, cucurbit[7]uril (CB[7]) interactions with guest-linked input sequences. Since control of the strand-displacement process is salient, we demonstrate how HG-TMSD can be finely modulated via changes to the structure of the input sequence (including synthetic guest head-group and/or linker length). Further, for a given input sequence, competing small-molecule guests can serve as effective regulators (with fine and coarse control) of HG-TMSD. To show integration into functional devices, we have incorporated HG-TMSD into machines that control enzyme activity and layered reactions that detect specific microRNA.

Synthesis and Applications of Porphyrin-Biomacromolecule Conjugates.

With potential applications in materials and especially in light-responsive biomedicine that targets cancer tissue selectively, much research has focused on developing covalent conjugation techniques to tether porphyrinoid units to various biomacromolecules. This review details the key synthetic approaches that have been employed in the recent decades to conjugate porphyrinoids with oligonucleotides and peptides/proteins. In addition, we provide succinct discussions on the subsequent applications of such hybrid systems and also give a brief overview of the rapidly progressing field of porphyrin-antibody conjugates. Since nucleic acid and peptide systems vary in structure, connectivity, functional group availability and placement, as well as stability and solubility, tailored synthetic approaches are needed for conjugating to each of these biomacromolecule types. In terms of tethering to ONs, porphyrins are typically attached by employing bioorthogonal chemistry (e.g., using phosphoramidites) that drive solid-phase ON synthesis or by conducting post-synthesis modifications and subsequent reactions (such as amide couplings, hydrazide-carbonyl reactions, and click chemistry). In contrast, peptides and proteins are typically conjugated to porphyrinoids using their native functional groups, especially the thiol and amine side chains. However, bioorthogonal reactions (e.g., Staudinger ligations, and copper or strain promoted alkyne-azide cycloadditions) that utilize de novo introduced functional groups onto peptides/proteins have seen vigorous development, especially for site-specific peptide-porphyrin tethering. While the ON-porphyrin conjugates have largely been explored for programmed nanostructure self-assembly and artificial light-harvesting applications, there are some reports of ON-porphyrin systems targeting clinically translational applications (e.g., antimicrobial biomaterials and site-specific nucleic acid cleavage). Conjugates of porphyrins with proteinaceous moieties, on the other hand, have been predominantly used for therapeutic and diagnostic applications (especially in photodynamic therapy, photodynamic antimicrobial chemotherapy, and photothermal therapy). The advancement of the field of porphyrinoid-bioconjugation chemistry from basic academic research to more clinically targeted applications require continuous fine-tuning in terms of synthetic strategies and hence there will continue to be much exciting work on porphyrinoid-biomacromolecule conjugation.

Effect of change in tidal volume on left to right shunt across ventricular septal defect in children - A pilot study.

BACKGROUND: Pulmonary vascular resistance, an important determinant of shunting across ventricular septal defects (VSD), rises at both extremes of lung volume. AIMS: We sought to determine the effect of changes in tidal volumes (VT) on pulmonary blood flow (Qp), systemic blood flow (Qs), and shunt (Qp/Qs) in children with VSD. SETTING: Single-center teaching hospital. DESIGN: Prospective observational study. METHODS: Thirty children with a mean age of 11.8 ± 5 months undergoing surgical closure of VSD were studied. Hemodynamics and shunt-related parameters were assessed using transthoracic echocardiography measured at three different VT i.e. 10, 8, and 6-ml/kg keeping the minute ventilation constant. RESULTS: Reduction in VT from 10 to 8 to 6 ml/kg led to a reduction in gradient across VSD measuring 23.5, 20 and 13 mmHg respectively (P < 0.001). Similarly, right ventricluar outflow tract (RVOT) diameter, RVOT velocity time integral, Qp (57.3 ± 18.1, 50.6 ± 16.9, 39.9 ± 14.7 mL; P < 0.001), Qs (24.1 ± 10.4, 20.0 ± 8.7, 15.3 ± 6.9 mL; P < 0.001) and peak airway pressure (17.2 ± 1.5, 15.8 ± 1.3, 14.5 ± 1.2 cmHg; P < 0.001) showed progressive decline with decreasing VT from 10 to 8 to 6 ml/kg, respectively. However, Qp/Qs (2.4 ± 0.4, 2.6 ± 0.4, 2.6 ± 0.4) demonstrated a minor increasing trend. CONCLUSION: Lower VT reduces the gradient across VSD, the pulmonary blood flow, and the peak airway pressure. Hence, ventilation with lower VT and higher respiratory rate maintaining adequate minute ventilation might be preferable in children with VSD. Further studies are required to confirm the findings of this pilot study.

Bright G-Quadruplex Nanostructures Functionalized with Porphyrin Lanterns.

The intricate arrangement of numerous and closely placed chromophores on nanoscale scaffolds can lead to key photonic applications ranging from optical waveguides and antennas to signal-enhanced fluorescent sensors. In this regard, the self-assembly of dye-appended DNA sequences into programmed photonic architectures is promising. However, the dense packing of dyes can result in not only compromised DNA assembly (leading to ill-defined structures and precipitates) but also to essentially nonfluorescent systems (due to π-π aggregation). Here, we introduce a two-step "tether and mask" strategy wherein large porphyrin dyes are first attached to short G-quadruplex-forming sequences and then reacted with per-O-methylated ß-cyclodextrin (PMßCD) caps, to form supramolecular synthons featuring the porphyrin fluor fixed into a masked porphyrin lantern (PL) state, due to intramolecular host-guest interactions in water. The PL-DNA sequences can then be self-assembled into cyclic architectures or unprecedented G-wires tethered with hundreds of porphyrin dyes. Importantly, despite the closely arrayed PL units (∼2 nm), the dyes behave as bright chromophores (up to 180-fold brighter than the analogues lacking the PMßCD masks). Since other self-assembling scaffolds, dyes, and host molecules can be used in this modular approach, this work lays out a general strategy for the bottom-up aqueous self-assembly of bright nanomaterials containing densely packed dyes.

Host-Guest Tethered DNA Transducer: ATP Fueled Release of a Protein Inhibitor from Cucurbit[7]uril.

Host-guest complexes are emerging as powerful components in functional systems with applications ranging from materials to biomedicine. In particular, CB7 based host-guest complexes have received much attention for the controlled release of drugs due to the remarkable ability of CB7 toward binding input molecules in water with high affinity leading to displacement of CB7 from included pharmacophores (or from drug loaded porous particles). However, the release of bound guests from CB7 in response to endogenous biological molecules remains limited since the input biomolecule needs to have the appropriate chemical structure to bind tightly into the CB7 cavity. Herein we describe a synthetic transducer based on self-assembling DNA-small molecule chimeras (DCs) that is capable of converting a chosen biological input, adenosine triphosphate (ATP; that does not directly bind to the CB7 host), into functional displacement of a protein inhibitor that is bound within the CB7 host. Our system-which features the first example of a covalent CB-DNA conjugate-is highly modular and can be adapted to enable responsiveness to other biologically/clinically relevant stimuli via its split DNA aptamer architecture.