An electrochemical aptasensor for Δ-tetrahydrocannabinol detection in saliva on a microfluidic platform.

We present a novel "on-off", cost-effective, rapid electrochemical aptasensor combined with a microfluidics cartridge system for the detection of Δ-THC (Δ-tetrahydrocannabinol) in human saliva via differential pulse voltammetry. The assay relied on the competitive binding between the Δ-THC and a soluble redox indicator methylene blue, using an aptamer selected via FRELEX. We found that the aptasensor can detected 1 nM of Δ-THC in PBS in a three-electrode cell system, while the sensitivity and both the dissociation constant (K) and association constant (K) were dependent on the aptamer density.

Molecular modeling in the design of peptidomimetics and peptide surrogates.

The most important natural sources of new leads are plant extracts, bacterial broths, animal venoms and peptides isolated from living organisms. However, only the three first have been used extensively in the development of new therapeutic agents. This is probably due to the low pharmacological profile exhibited by peptides, that requires a lengthy transformation to make them suitable as new leads.

Identification of selective inhibitors of acetylcholinesterase from a combinatorial library of 2,5-piperazinediones.

The potentiation of central cholinergic activity has been proposed as a therapeutic approach for improving cognitive function in patients with Alzheimer's disease. Increasing the acetylcholine concentration in brain by modulating acetylcholinesterase (AChE) activity is among the most promising strategies. We have used a combinatorial approach to identify different 2,5-piperazinediones (DKP) with AChE inhibitory activity.

Differential binding mode of diverse cyclooxygenase inhibitors.

Non-steroidal anti-inflammatory drugs (NSAIDs) are competitive inhibitors of cyclooxygenase (COX), the enzyme that mediates biosynthesis of prostaglandins and thromboxanes from arachidonic acid. There are at least two different isoforms of the enzyme known as COX-1 and -2. Site directed mutagenesis studies suggest that non-selective COX inhibitors of diverse chemical families exhibit differential binding modes to the two isozymes.

Toward the design of chemical libraries for mass screening biased against mutagenic compounds.

The ability to develop a chemical into a drug depends on multiple factors. Beyond potency and selectivity, ADME/PK and the toxicological profile of the compound play a significant role in its evaluation as a candidate for development. Those factors are being brought into bear earlier in the discovery process and even into the design of libraries for screening.