biebele abel | Morgan State University (original) (raw)

Papers by biebele abel

Biomolecules

The lipid composition of biomembranes influences the properties of the lipid bilayer and that of ... more The lipid composition of biomembranes influences the properties of the lipid bilayer and that of the proteins. In this study, the lipidome and the lipid/protein ratio of membranes from High Five™ insect cells overexpressing mouse P-glycoprotein was characterized. This provides a better understanding of the lipid environment in which P-glycoprotein is embedded, and thus of its functional and structural properties. The relative abundance of the distinct phospholipid classes and their acyl chain composition was characterized. A mass ratio of 0.57 ± 0.11 phospholipids to protein was obtained. Phosphatidylethanolamines are the most abundant phospholipids, followed by phosphatidylcholines. Membranes are also enriched in negatively charged lipids (phosphatidylserines, phosphatidylinositols and phosphatidylglycerols), and contain small amounts of sphingomyelins, ceramides and monoglycosilatedceramides. The most abundant acyl chains are monounsaturated, with significant amounts of saturated ...

Proceedings of the National Academy of Sciences

P-glycoprotein (P-gp), also known as ABCB1, is a cell membrane transporter that mediates the effl... more P-glycoprotein (P-gp), also known as ABCB1, is a cell membrane transporter that mediates the efflux of chemically dissimilar amphipathic drugs and confers resistance to chemotherapy in most cancers. Homologous transmembrane helices (TMHs) 6 and 12 of human P-gp connect the transmembrane domains with its nucleotide-binding domains, and several residues in these TMHs contribute to the drug-binding pocket. To investigate the role of these helices in the transport function of P-gp, we substituted a group of 14 conserved residues (seven in both TMHs 6 and 12) with alanine and generated a mutant termed 14A. Although the 14A mutant lost the ability to pump most of the substrates tested out of cancer cells, surprisingly, it acquired a new function. It was able to import four substrates, including rhodamine 123 (Rh123) and the taxol derivative flutax-1. Similar to the efflux function of wild-type P-gp, we found that uptake by the 14A mutant is ATP hydrolysis-, substrate concentration-, and t...

Journal of medicinal chemistry, Jan 8, 2018

A novel set of 64 analogues based on our lead compound 1 was designed and synthesized with an ini... more A novel set of 64 analogues based on our lead compound 1 was designed and synthesized with an initial objective of understanding the structural requirements of ligands binding to a highly perplexing substrate-binding site of P-glycoprotein (P-gp) and their effect on modulating the ATPase function of the efflux pump. Compound 1, a stimulator of P-gp ATPase activity, was transformed to ATPase inhibitory compounds 39, 53, and 109. The ATPase inhibition by these compounds was predominantly contributed by the presence of a cyclohexyl group in lieu of the 2-aminobenzophenone moiety of 1. The 4,4-difluorocyclohexyl analogues, 53 and 109, inhibited the photolabeling by [125I]-IAAP, with IC50 values of 0.1 and 0.76 μM, respectively. Selected compounds were shown to reverse paclitaxel resistance in HEK293 cells overexpressing P-gp and were selective toward P-gp over CYP3A4. Induced-fit docking highlighted a plausible binding pattern of inhibitory compounds in the putative-binding pocket of P-...

The Journal of biological chemistry, Jan 10, 2017

P-glycoprotein (P-gp) is a multidrug transporter that utilizes energy from ATP hydrolysis to effl... more P-glycoprotein (P-gp) is a multidrug transporter that utilizes energy from ATP hydrolysis to efflux a variety of structurally dissimilar hydrophobic and amphipathic compounds including anticancer drugs from cells. Several structural studies on purified P-gp have been reported and there is very limited and in some cases conflicting information available on ligand interactions with isolated transporter in a dodecyl maltoside detergent environment. In this report, we compare the biochemical properties of human and mouse P-gp in native membranes, detergent micelles, and after reconstitution in artificial membranes. We found that the modulators zosuquidar, tariquidar and elacridar stimulated the ATPase activity of purified human or mouse P-gp in a detergent micelle environment, whereas these drugs inhibited the ATPase activity of the transporter in native membranes or when it was reconstituted in proteoliposomes, with IC50 values in the 10 to 40 nanomolar range. Similarly, a 30- to 150-f...

Nano Biomedicine and Engineering, 2015

We report the enhancement of chemiluminescence response of horseradish peroxidase (HRP) in bioass... more We report the enhancement of chemiluminescence response of horseradish peroxidase (HRP) in bioassays by plasmonic surfaces, which are comprised of (i) silver island films (SIFs) and (ii) metal thin films (silver, gold, copper, and nickel, 1 nm thick) deposited onto glass slides. A model bioassay, based on the interactions of avidin-modified HRP with a monolayer of biotinylated poly(ethylene-glycol)-amine, was employed to evaluate the ability of plasmonic surfaces to enhance chemiluminescence response of HRP. Chemiluminescence response of HRP in model bioassays were increased up to ~3.7-fold as compared to the control samples (i.e. glass slides without plasmonic nanoparticles), where the largest enhancement of the chemiluminescence response was observed on SIFs with high loading. These findings allowed us to demonstrate the use of SIFs (high loading) for the detection of a biologically relevant target protein (glial fibrillary acidic protein or GFAP), where the chemiluminescence response of the standard bioassay for GFAP was enhanced up to ~50% as compared to bioassay on glass slides.

Nano biomedicine and engineering

In this study, we demonstrated a unique application of our Metal-Assisted and Microwave-Accelerat... more In this study, we demonstrated a unique application of our Metal-Assisted and Microwave-Accelerated Evaporative Crystallization (MA-MAEC) technique for the de-crystallization of uric acid crystals, which causes gout in humans when monosodium urate crystals accumulate in the synovial fluid found in the joints of bones. Given the shortcomings of the existing treatments for gout, we investigated whether the MA-MAEC technique can offer an alternative solution to the treatment of gout. Our technique is based on the use of metal nanoparticles (i.e., gold colloids) with low microwave heating to accelerate the de-crystallization process. In this regard, we employed a two-step process; (i) crystallization of uric acid on glass slides, which act as a solid platform to mimic a bone, (ii) de-crystallization of uric acid crystals on glass slides with the addition of gold colloids and low power microwave heating, which act as "nano-bullets" when microwave heated in a solution. We observ...

Journal of immunological methods, 2014

Portugaliae Electrochimica Acta, 2012

Cyclic voltammetry was used in cetyltrimethylammonium bromide (CTAB) micellar solution to determi... more Cyclic voltammetry was used in cetyltrimethylammonium bromide (CTAB) micellar solution to determine the half-wave potentials of selected chlorophenols, CPs. It is observed that all the electrochemical parameters of the studied CPs decrease with an increase in the number of chlorine atom(s) attached to the parent compound. The mathematical relationship between the obtained E 1/2 and the number of chlorine atoms in the parent compound is given. The formal potentials, E 0' , of the CPs are approximated from the obtained half-wave potentials.

In this study, we report the use of an enzyme-based hybrid platform, which is comprised of silver... more In this study, we report the use of an enzyme-based hybrid platform, which is comprised of silver island films, enzymes (HRP and AP) and high-throughput screening (HTS) microplates, to enhance the colorimetric response of enzymatic reactions. The hybrid platform was designed in a two-step process: (i) deposition of SIFs onto HTS microplates with low, medium, and high loading (refers to the extent of the surface plasmon resonance peak of SIFs at 460 nm) using Tollen&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s reaction scheme; and (ii) attachment of b-BSA or BEA as linkers for the immobilization of enzymes. The presence of SIFs within the wells of the HTS microplates was confirmed using an optical spectrophotometer and real-color photography. Control experiments, where SIFs were omitted from the surfaces were carried out to confirm the effect of SIFs on the enzymatic colorimetric response. Significant colorimetric signal enhancement was observed for HRP or AP on SIFs (high loading) deposited HTS microplates using b-BSA (up to ~3-fold for AP and ~6-fold HRP) or BEA (up to ~7-fold for both HRP and AP), as compared to our control samples. The observed increase in colorimetric response can be attributed to the nature of BEA, which exposes surface-bound enzymes to the substrate present in bulk more efficiently than b-BSA. This study proves that SIFs can serve as a valuable tool to improve the signal output of existing bioassays carried out in HTS microplates, which can be applicable to the field biosensors and plasmonics.