Wu Su

DNA‐Templated Photonic Arrays and Assemblies: Design Principles and Future Opportunities

Molecular photonics is a rapidly developing and multi-disciplinary field of research involving the construction of molecular assemblies comprising photoactive building blocks that are responsive to a light stimulus. A salient challenge in this field is the controlled assembly of these building blocks with nanoscale precision. DNA exhibits considerable promise as an architecture for the templated assembly of photoactive materials. In this Concept Article we describe the progress that has been made in the area of DNA photonics, in which DNA acts as a platform for the construction of optoelectronic assemblies, thin films and devices.

Site‐Specific Assembly of DNA‐Based Photonic Wires by Using Programmable Polyamides

The first example of a programmable DNA photonic wire is reported utilizing fluorophore-tethered pyrrole-imidazole polyamides for site-directed fluorophore assembly along a pre-formed DNA duplex (see scheme; PB=Pacific Blue, Cy3=Cyanine 3; orange rectangles=fluorophore). The importance of such control is revealed by efficient energy transport over distances in excess of 27 nm.

Directed assembly of DNA-functionalized gold nanoparticles using pyrrole-imidazole polyamides.

Traditional methods for the construction of nanoparticle arrays and lattices exploit Watson-Crick base pairing of single-stranded DNA sequences as a proxy for self-assembly. Although this approach has been utilized in a variety of applications in nanoassembly, diagnostics, and biomedicine, the diversity of this recognition lexicon could be considerably increased by developing strategies that recognize the base-pairing landscape of double-stranded DNA (dsDNA) sequences. Herein we describe the first report of programmed gold nanoparticle (GNP) aggregation directed by the recognition of dsDNA sequences using pyrrole-imidazole polyamide-GNP (PA-GNP) conjugates. We demonstrate the reversibility and selectivity of this strategy for forming GNP aggregates in the presence of fully matched dsDNA sequences relative to dsDNA sequences containing one- and two-base-pair mismatches.

Highly Size‐ and Shape‐Controlled Synthesis of Silver Nanoparticles via a Templated Tollens Reaction

A mild, facile one-step synthetic strategy for the preparation of size-and shape-controlled silver nanoparticles (AgNPs) is presented. The high degree of size-and shape-control of these AgNPs is achieved by the use of triazole sugar ligands scaffolded by a central resorcinol ether core. Both the triazoles and the resorcinol ether core mediate the nucleation, growth, and passivation phases of the preparation of AgNP in the presence of the Tollens reagent as the silver source. Kinetic and 1H NMR titration data is presented describing the nature of the interactions between the Tollens reagent and these ligands.

Synthesis and structure–activity relationship studies of teixobactin analogues

A new series of teixobactin analogues were synthesized via an oxidative cyclative cleavage approach using aryl hydrazide resin as the solid support. Structure–activity relationship studies revealed that the guanidine or amine group at position 10, the hydroxyl group of Ser7 residue and the NH proton of the N-terminal Phe1 residue are critical to the antibacterial activities, while side chain size and functional group changes are tolerated at position 4. These findings will facilitate the development of new teixobactin analogues with enhanced pharmacological properties.

Catalytic Asymmetric Inverse-Electron-Demand 1,3-Dipolar Cycloaddition of C,N-Cyclic Azomethine Imines with Azlactones: Access to Chiral Tricyclic Tetrahydroisoquinolines.

Reported herein is a bifunctional-organocatalyst-mediated enantioselective inverse-electron-demand 1,3-dipolar cycloaddition of C,N-cyclic azomethine imines with azlactones. The strategy provides concise access to enantioenriched C1-substituted tetrahydroisoquinolines featuring a pyrazolidinone scaffold. Moreover, the scalability and practical utility of this protocol was well demonstrated by employing a gram-scale reaction and some representative transformations.

Highly efficient synthesis of DNA-binding hairpin polyamides via the use of a new triphosgene coupling strategy

A facile and highly efficient solid phase synthesis method is reported for the preparation of hairpin DNA-binding polyamides using the cost-effective triphosgene (BTC) activating agent. Difficult polyamide sequences were prepared from N-methylimidazole (Im) and N-methylpyrrole (Py) building blocks with high stepwise yields (>98%) using Boc chemistry. The versatility of the triphosgene coupling approach was also demonstrated for the first time on aryl hydrazine resins to afford biomedically relevant tail-truncated polyamides in excellent isolated yields.

Efficient Synthesis and Stereochemical Revision of Coibamide A

Coibamide A is a highly potent antiproliferative cyclodepsipeptide originally isolated from a Panamanian marine cyanobacterium. Herein we report an efficient solid-phase strategy for assembly of highly N-methylated cyclodepsipeptides, which is invaluable in generating coibamide A derivatives for structure-activity relationship studies. As a consequence of our synthetic studies, two stereochemical assignments of coibamide A were revised and the total synthesis of this natural compound was achieved for the first time.

Addressable and unidirectional energy transfer along a DNA three-way junction programmed by pyrrole-imidazole polyamides

We describe a photonic waveguide where FRET is routed uni-directionally along a double-stranded DNA track. The efficiency of FRET is modulated by the supramolecular control of fluorophores along double-stranded DNA using fluorophore-tethered Pyrrole-Imidazole polyamides (PAs). We show that uni-directional FRET is enhanced by the complete assembly of each of the constituent parts, resulting in the selective routing of light along simple DNA duplexes as well as a three-way junction (3WJ).

NUMB negatively regulates the epithelial-mesenchymal transition of triple-negative breast cancer by antagonizing Notch signaling

Triple-negative breast cancer (TNBC), an aggressive subtype of breast cancer with higher rates of early relapse and metastasis, is frequently associated with aberrant activation of epithelial-mesenchymal transition (EMT). Nonetheless, how EMT is initiated and regulated during TNBC progression is not well understood. Here, we report that NUMB is a negative regulator of EMT in both human mammary epithelial cells and breast cancer cells. Reduced NUMB expression was significantly associated with elevated EMT in TNBC. Conversely, overexpression of NUMB strongly attenuated the EMT program and metastasis of TNBC cell lines. Interestingly, we showed that NUMB employs different molecular mechanisms to regulate EMT. In normal mammary epithelial cells and breast cancer cells expressing wild-type p53, NUMB suppressed EMT by stabilizing p53. However, in TNBC cells, loss of NUMB facilitated the EMT program by activating Notch signaling. Consistent with these findings, low NUMB expression and high Notch activity were significantly correlated with the TNBC subtype in patients. Collectively, these findings reveal novel molecular mechanisms of NUMB in the regulation of breast tumor EMT, especially in TNBC.