Monoclonal antibodies (mAbs) are one of the most lucrative pharmacologics currently on the market due to their diverse array of applications. However, the diversity of these therapeutics is often limited...
Rapid and effective differentiation
and quantification of a small
molecule drug, such as fentanyl, in bodily fluids are major challenges
for diagnosis and personal medication. However, the current toxicology
methods used to measure drug concentration and metabolites require
laboratory-based testing, which is not an efficient or cost-effective
way to treat patients in a timely manner. Here, we show an assay for
monitoring fentanyl levels by combining the intermolecular interaction-enabled
small molecule recognition (iMSR) with differential impedance analysis
of conjugated polymers. The differential interactions with the designed
anchor interface were transduced through the perturbance of the electric
status of the flexible conducting polymer. This assay showed excellent
fentanyl selectivity against common interferences, as well as in variable
body fluids through either testing strips or skin patches. Directly
using the patient blood, the sensor provided 1%–5% of the average
deviation compared to the “gold” standard method LC-MS
results in the medically relevant fentanyl range of 20–90 nM.
The superior sensing properties, in conjunction with mechanical flexibility
and compatibility, enabled point-of-care detection and provided a
promising avenue for applications beyond the scope of biomarker detection.
Protein deamidation is a degradation mechanism that significantly
impacts both pharmaceutical and physiological proteins. Deamidation
impacts two amino acids, Asn and Gln, where the net neutral residues
are converted into their acidic forms. While there are multiple similarities
between the reaction mechanisms of the two residues, the impact of
Gln deamidation has been noted to be most significant on physiological
proteins while Asn deamidation has been linked to both pharmaceutical
and physiological proteins. For this purpose, we sought to analyze
the thermochemical and kinetic properties of the different reactions
of Gln deamidation relative to Asn deamidation. In this study, we
mapped the deamidation of Gln-X dipeptides into Glu-X dipeptides using
density functional theory (DFT). Full network mapping facilitated
the prediction of reaction selectivity between the two primary pathways,
as well as between the two products of Gln-X deamidation as a function
of solvent dielectric. To achieve this analysis, we studied a total
of 77 dipeptide reactions per solvent dielectric (308 total reactions).
Modeled at a neutral pH and using quantum chemical and statistical
thermodynamic methods, we computed the following values: enthalpy
of reaction (ΔH
RXN), entropy (ΔS
RXN), Gibbs free energy of reaction (ΔG
RXN), activation energy (E
A), and the Arrhenius preexponential factor (log(A)) for each
dipeptide. Additionally, using chemical reaction principles, we generated
a database of computed rate coefficients for all possible N-terminus
Gln-X deamidation reactions at a neutral pH, predicted the most likely
deamidation reaction mechanism for each dipeptide reaction, analyzed
our results against our prior study on Asn-X deamidation, and matched
our results against qualitative trends previously noted by experimental
literature.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.