Self-assembling multidomain peptides have been shown to have desirable properties, such as the ability to form hydrogels that rapidly recover following shear-thinning and the potential to be tailored by amino acid selection to vary their elasticity and encapsulate and deliver proteins and cells. Here we describe the effects of substitution of aliphatic hydrophobic amino acids in the central domain of the peptide for the aromatic amino acids phenylalanine, tyrosine, and tryptophan. While the basic nanofibrous morphology is retained in all cases, selection of the particular core residues results in switching from antiparallel hydrogen bonding to parallel hydrogen bonding in addition to changes in nanofiber morphology and in hydrogel rheological properties. Peptide nanofiber assemblies are investigated by circular dichroism polarimetry, infrared spectroscopy, atomic force microscopy, transmission and scanning electron microscopy, oscillatory rheology, and molecular dynamics simulations. Results from this study will aid in designing next generation cell scaffolding materials.
Tianeptine is a tricyclic anti-depressant that is also known to have opioid receptor activity. We present two fatal cases of tianeptine intoxication in Texas in which tianeptine was used recreationally. The first case involved a 28-year-old white male found alone on the floor of his locked residence. He had a history of drug abuse but no other toxicological findings. The second case involved a 30-year-old white male found on the floor of the bathroom in his home. Drug paraphernalia and bags labeled as tianeptine powder were found at both scenes. In response to the first case, our laboratory developed a method for quantitation of tianeptine by LC–MS-MS. This method was then validated according to SWGTOX guidelines for specificity, calibration model, limit of detection, limit of quantitation, accuracy, precision, ion suppression, and carryover. This method was successfully used to determine tianeptine concentrations in postmortem blood in two cases. In these cases, tianeptine was measured at 2.0 mg/L and 8.4 mg/L. These represent the first known tianeptine fatalities in Texas and in the United States.
Modafinil (brand name Provigil®) is a Schedule IV (U.S.) drug used for the treatment of narcolepsy and sleep disorders. It is also known to be used recreationally. Analogs of modafinil, including adrafinil, remain unapproved and/or unscheduled. The lack of scheduling has made these analogs a popular target for recreational use and inclusion in dietary supplements. However, the use of controlled substances (or their analogs) without the care of a physician presents a public health risk. Preliminary nontargeted analyses in our laboratory revealed the presence of adrafinil in several dietary supplements, highlighting the need for an analytical method to identify modafinil analogs in supplements. A liquid chromatography high resolution mass spectrometry (LC-HRMS) method was developed and validated to quantitate modafinil, plus four novel unscheduled modafinil analogs: adrafinil, CRL-40,940, CRL-40,941, and N-methyl-4,4-difluoromodafinil. This method was then applied to four samples of products marketed as dietary supplements collected via undercover purchase. These four products were marketed as nootropics or cognitive enhancers and labeled to contain adrafinil. Adrafinil was found in all four samples. The identification of modafinil analogs in this context is important so that consumers are not, knowingly or unknowingly, consuming these active pharmaceutical ingredients in products marketed as dietary supplements.
13 August 2020 in Journal of Agricultural and Food Chemistry