Multivalent benzoboroxole functionalized polymers as gp120 glycan targeted microbicide entry inhibitors.

Microbicides are women-controlled prophylactics for sexually transmitted infections. The most important class of microbicides target HIV-1 and contain antiviral agents formulated for topical vaginal delivery. Identification of new viral entry inhibitors that target the HIV-1 envelope is important because they can inactivate HIV-1 in the vaginal lumen before virions can come in contact with CD4+ cells in the vaginal mucosa. Carbohydrate binding agents (CBAs) demonstrate the ability to act as entry inhibitors due to their ability to bind to glycans and prevent gp120 binding to CD4+ cells. However, as proteins they present significant challenges in regard to economical production and formulation for resource-poor environments. We have synthesized water-soluble polymer CBAs that contain multiple benzoboroxole moieties. A benzoboroxole-functionalized monomer was synthesized and incorporated into linear oligomers with 2-hydroxypropylmethacrylamide (HPMAm) at different feed ratios using free radical polymerization. The benzoboroxole small molecule analogue demonstrated weak affinity for HIV-1BaL gp120 by SPR; however, the 25 mol % functionalized benzoboroxole oligomer demonstrated a 10-fold decrease in the K(D) for gp120, suggesting an increased avidity for the multivalent polymer construct. High molecular weight polymers functionalized with 25, 50, and 75 mol % benzoboroxole were synthesized and tested for their ability to neutralize HIV-1 entry for two HIV-1 clades and both R5 and X4 coreceptor tropism. All three polymers demonstrated activity against all viral strains tested with EC(50)s that decrease from 15000 nM (1500 microg mL(-1)) for the 25 mol % functionalized polymers to 11 nM (1 microg mL(-1)) for the 75 mol % benzoboroxole-functionalized polymers. These polymers exhibited minimal cytotoxicity after 24 h exposure to a human vaginal cell line.

In situ synthesis of DNA microarray on functionalized cyclic olefin copolymer substrate.

Thermoplastic materials such as cyclic-olefin copolymers (COC) provide a versatile and cost-effective alternative to the traditional glass or silicon substrate for rapid prototyping and industrial scale fabrication of microdevices. To extend the utility of COC as an effective microarray substrate, we developed a new method that enabled for the first time in situ synthesis of DNA oligonucleotide microarrays on the COC substrate. To achieve high-quality DNA synthesis, a SiO(2) thin film array was prepatterned on the inert and hydrophobic COC surface using RF sputtering technique. The subsequent in situ DNA synthesis was confined to the surface of the prepatterned hydrophilic SiO(2) thin film features by precision delivery of the phosphoramidite chemistry using an inkjet DNA synthesizer. The in situ SiO(2)-COC DNA microarray demonstrated superior quality and stability in hybridization assays and thermal cycling reactions. Furthermore, we demonstrate that pools of high-quality mixed-oligos could be cleaved off the SiO(2)-COC microarrays and used directly for construction of DNA origami nanostructures. It is believed that this method will not only enable synthesis of high-quality and low-cost COC DNA microarrays but also provide a basis for further development of integrated microfluidics microarrays for a broad range of bioanalytical and biofabrication applications.

Phase transfer catalysts drive diverse organic solvent solubility of single-walled carbon nanotubes helically wrapped by ionic, semiconducting polymers.

Use of phase transfer catalysts such as 18-crown-6 enables ionic, linear conjugated poly[2,6-{1,5-bis(3-propoxysulfonicacidsodiumsalt)}naphthylene]ethynylene (PNES) to efficiently disperse single-walled carbon nanotubes (SWNTs) in multiple organic solvents under standard ultrasonication methods. Steady-state electronic absorption spectroscopy, atomic force microscopy (AFM), and transmission electron microscopy (TEM) reveal that these SWNT suspensions are composed almost exclusively of individualized tubes. High-resolution TEM and AFM data show that the interaction of PNES with SWNTs in both protic and aprotic organic solvents provides a self-assembled superstructure in which a PNES monolayer helically wraps the nanotube surface with periodic and constant morphology (observed helical pitch length = 10 ± 2 nm); time-dependent examination of these suspensions indicates that these structures persist in solution over periods that span at least several months. Pump-probe transient absorption spectroscopy reveals that the excited state lifetimes and exciton binding energies of these well-defined nanotube-semiconducting polymer hybrid structures remain unchanged relative to analogous benchmark data acquired previously for standard sodium dodecylsulfate (SDS)-SWNT suspensions, regardless of solvent. These results demonstrate that the use of phase transfer catalysts with ionic semiconducting polymers that helically wrap SWNTs provide well-defined structures that solubulize SWNTs in a wide range of organic solvents while preserving critical nanotube semiconducting and conducting properties.

Inkless microcontact printing on SAMs of Boc- and TBS-protected thiols.

We report a new inkless catalytic muCP technique that achieves accurate, fast, and complete pattern reproduction on SAMs of Boc- and TBS-protected thiols immobilized on gold using a polyurethane-acrylate stamp functionalized with covalently bound sulfonic acids. Pattern transfer is complete at room temperature just after one minute of contact and renders sub-200 nm size structures of chemically differentiated SAMs.

Injectable laminin-functionalized hydrogel for nucleus pulposus regeneration.

Cell delivery to the pathological intervertebral disc (IVD) has significant therapeutic potential for enhancing IVD regeneration. The development of injectable biomaterials that retain delivered cells, promote cell survival, and maintain or promote an NP cell phenotype in vivo remains a significant challenge. Previous studies have demonstrated NP cell - laminin interactions in the nucleus pulposus (NP) region of the IVD that promote cell attachment and biosynthesis. These findings suggest that incorporating laminin ligands into carriers for cell delivery may be beneficial for promoting NP cell survival and phenotype. Here, an injectable, laminin-111 functionalized poly(ethylene glycol) (PEG-LM111) hydrogel was developed as a biomaterial carrier for cell delivery to the IVD. We evaluated the mechanical properties of the PEG-LM111 hydrogel, and its ability to retain delivered cells in the IVD space. Gelation occurred in approximately 20 min without an initiator, with dynamic shear moduli in the range of 0.9-1.4 kPa. Primary NP cell retention in cultured IVD explants was significantly higher over 14 days when cells were delivered within a PEG-LM111 carrier, as compared to cells in liquid suspension. Together, these results suggest this injectable laminin-functionalized biomaterial may be an easy to use carrier for delivering cells to the IVD.