Biomedical subjects

Alan T Johnson

Publications and source records attributed to Alan T Johnson.

6 recordsLinked to original sources

PubMed2006

Synthetic small molecule furin inhibitors derived from 2,5-dideoxystreptamine.

Furin plays a crucial role in embryogenesis and homeostasis and in diseases such as Alzheimer's disease, cancer, and viral and bacterial infections. Thus, inhibition of furin may provide a feasible and promising approach for therapeutic intervention of furin-mediated disease mechanisms. Here, we report on a class of small molecule furin inhibitors based on 2,5-dideoxystreptamine. Derivatization of 2,5-dideoxystreptamine by the addition of guanidinylated aryl groups yielded a set of furin inhibitors with nanomolar range potency against furin when assayed in a biochemical cleavage assay. Moreover, a subset of these furin inhibitors protected RAW 264.7 macrophage cells from toxicity caused by furin-dependent processing of anthrax protective antigen. These inhibitors were found to behave as competitive inhibitors of furin and to be relatively specific for furin. Molecular modeling revealed that these inhibitors may target the active site of furin as they showed site occupancy similar to the alkylating inhibitor decanoyl-Arg-Val-Lys-Arg-CH(2)Cl. The compounds presented here are bona fide synthetic small molecule furin inhibitors that exhibit potency in the nanomolar range, suggesting that they may serve as valuable tools for studying furin action and potential therapeutics agents for furin-dependent diseases.

Animals↗

PubMed2006

Clean electromigrated nanogaps imaged by transmission electron microscopy.

Electromigrated nanogaps have shown great promise for use in molecular scale electronics. We have fabricated nanogaps on free-standing transparent SiN(x) membranes which permit the use of transmission electron microscopy (TEM) to image the gaps. The electrodes are formed by extending a recently developed controlled electromigration procedure and yield a nanogap with approximately 5 nm separation clear of any apparent debris. The gaps are stable, on the order of hours as measured by TEM, but over time (months) relax to about 20 nm separation determined by the surface energy of the Au electrodes. A major benefit of electromigrated nanogaps on SiN(x) membranes is that the junction pinches in away from residual metal left from the Au deposition which could act as a parasitic conductance path. This work has implications to the design of clean metallic electrodes for use in nanoscale devices where the precise geometry of the electrode is important.

Journal Article↗

PubMed2005

Electronic devices based on purified carbon nanotubes grown by high-pressure decomposition of carbon monoxide.

The excellent properties of transistors, wires and sensors made from single-walled carbon nanotubes (SWNTs) make them promising candidates for use in advanced nanoelectronic systems. Gas-phase growth procedures such as the high-pressure decomposition of carbon monoxide (HiPCO) method yield large quantities of small-diameter semiconducting SWNTs, which are ideal for use in nanoelectronic circuits. As-grown HiPCO material, however, commonly contains a large fraction of carbonaceous impurities that degrade the properties of SWNT devices. Here we demonstrate a purification, deposition and fabrication process that yields devices consisting of metallic and semiconducting nanotubes with electronic characteristics vastly superior to those of circuits made from raw HiPCO. Source-drain current measurements on the circuits as a function of temperature and backgate voltage are used to quantify the energy gap of semiconducting nanotubes in a field-effect transistor geometry. This work demonstrates significant progress towards the goal of producing complex integrated circuits from bulk-grown SWNT material.

Journal Article↗

PubMed2005

Synthesis of peapods using substrate-grown SWNTs and DWNTs: an enabling step toward peapod devices.

We report the successful synthesis of nanoscale peapods from single-walled and double-walled nanotubes grown by chemical vapor deposition (CVD) on substrates with windows etched into free-standing silicon nitride membranes. CVD-grown nanotubes were oxidized in air, then filled with C(60) molecules from the vapor phase. Observed variation in nanotube oxidation and C(60) packing with nanotube diameter agreed with theoretical expectations. Windowed samples provide several important advantages for property measurements of peapods and other nanomaterials. Individual nanostructures can be followed through processing steps, and a single nanostructure can be inspected by high-resolution TEM and subsequently contacted with nanoscale electrodes using electron beam lithography.

Journal Article↗

PubMed2005

High frequency scanning gate microscopy and local memory effect of carbon nanotube transistors.

We use impedance spectroscopy to measure the high-frequency properties of single-walled carbon nanotube field effect transistors (swCN-FETs). Furthermore, we extend scanning gate microscopy (SGM) to frequencies up to 15 MHz and use it to image changes in the impedance of swCN-FET circuits induced by the SGM tip gate. In contrast to earlier reports, the results of both experiments are consistent with a simple RC parallel circuit model of the swCN-FET, with a time constant of 0.3 micros. We also use the SGM tip to show the local nature of the memory effect normally observed in swCN-FETs, implying that nanotube-based memory cells can be miniaturized to dimensions of the order of tens of nm.

Electric Impedance↗

PubMed2005

DNA-decorated carbon nanotubes for chemical sensing.

We demonstrate a new, versatile class of nanoscale chemical sensors based on single-stranded DNA (ss-DNA) as the chemical recognition site and single-walled carbon nanotube field effect transistors (swCN-FETs) as the electronic read-out component. swCN-FETs with a nanoscale coating of ss-DNA respond to gas odors that do not cause a detectable conductivity change in bare devices. Responses of ss-DNA/swCN-FETs differ in sign and magnitude for different gases and can be tuned by choosing the base sequence of the ss-DNA. ss-DNA/swCN-FET sensors detect a variety of odors, with rapid response and recovery times on the scale of seconds. The sensor surface is self-regenerating: samples maintain a constant response with no need for sensor refreshing through at least 50 gas exposure cycles. This remarkable set of attributes makes sensors based on ss-DNA decorated nanotubes very promising for "electronic nose" and "electronic tongue" applications ranging from homeland security to disease diagnosis.

Base Sequence↗