A comparative analysis of current С-peptide assays compared to a reference method: can we overcome inertia to standardization?

Objectives: C-peptide is an equimolar by-product of insulin biosynthesis. It is used clinically to assess insulin secretion and differentiate types of diabetes. However, the lack of standardization across assays limits its broader application.

Physio-chemical Modifications to Re-engineer Small Extracellular Vesicles for Targeted Anticancer Therapeutics Delivery and Imaging.

Cancer theranostics developed through nanoengineering applications are essential for targeted oncologic interventions in the new era of personalized and precision medicine. Recently, small extracellular vesicles (sEVs) have emerged as an attractive nanoengineering platform for tumor-directed anticancer therapeutic delivery and imaging of malignant tumors. These natural nanoparticles have multiple advantages over synthetic nanoparticle-based delivery systems, such as intrinsic targeting ability, less immunogenicity, and a prolonged circulation time.

Comprehensive profiling and kinetic studies of glycated lysine residues in human serum albumin.

Lysine residues of proteins slowly react with glucose forming Amadori products. In hyperglycemic conditions, such as diabetes mellitus, this non-enzymatic glycation becomes more pervasive causing severe medical complications. The structure and conformation of a protein predisposes lysine sites to differing reactivity influenced by their steric availability and amino acid microenvironment.

Quantitation of glycated albumin by isotope dilution mass spectrometry.

Background: Glycated albumin is considered an alternative glycemic indicator in certain situations where HbA1c does not accurately reflect glycemic status. These patient cases are usually associated with decreased erythrocyte lifespan, gestational diabetes, or end-stage renal disease. The aim of our study was to develop an assay for absolute quantitation of glycated albumin based on isotope dilution liquid chromatography-mass spectrometry.

Higher degree of glycation of hemoglobin S compared to hemoglobin A measured by mass spectrometry: Potential impact on HbA1c testing.

Background: Glycated hemoglobin (GHb), reported as HbA1c, is used as marker of long-term glycemia for diabetic patients. HbA1c results from boronate affinity methods are generally considered to be unaffected by most hemoglobin variants; this assumes comparable glycation of variant and non-variant (HbAA) hemoglobins. In this report, glycation of HbA beta chain (βA) and HbS beta chain (βS) for the most common Hb variant trait (HbAS) are examined.

Two-step ion-exchange chromatographic purification combined with reversed-phase chromatography to isolate C-peptide for mass spectrometric analysis.

A liquid chromatography with mass spectrometry on-line platform that includes the orthogonal techniques of ion exchange and reversed phase chromatography is applied for C-peptide analysis. Additional improvement is achieved by the subsequent application of cation- and anion-exchange purification steps that allow for isolating components that have their isoelectric points in a narrow pH range before final reversed-phase mass spectrometry analysis. The utility of this approach for isolating fractions in the desired "pI window" for profiling complex mixtures is discussed.

Novel synthetic approach to charge-compensated phosphonio-nido-carboranes. Synthesis and structural characterization of neutral mono and bis(phosphonio) nido-ortho-carboranes.

A number of monosubstituted n-(triphenylphosphonio)-7,8-dicarba-nido-undecaboranes (2a, n = 1; 2b, n = 3; 2c, n = 5; 2d, n = 9) were prepared via a cross-coupling reaction between the tetrabutylammonium iodo-7,8-dicarba-nido-undecaborates (1a-d) and PPh3 in the presence of a Pd(PPh3)4 catalyst. The substitution rate was found to depend on the iodine position in the carborane cage. Under similar conditions, the reaction of 5,6-diiodo- (3) and 9,11-diiodo-7,8-dicarba-nido-undecaborate (5) anions exclusively yielded the monosubstitution products 5-iodo-6-(triphenylphosphonio)-7,8-dicarba-nido-undecaborane (4) and 9-iodo-11-(triphenylphosphonio)-7,8-dicarba-nido-undecaborane (6), respectively.

Carborane-derived local anesthetics are isomer dependent.

Clinically there is a need for local anesthetics with a greater specificity of action on target cells and longer duration. We have synthesized a series of local anesthetic derivatives we call boronicaines in which the aromatic phenyl ring of lidocaine was replaced with ortho-, meta-, C,C'-dimethyl meta- and para-carborane clusters. The boronicaine derivatives were tested for their analgesic activity and compared with lidocaine using standard procedures in mice following a plantar injection.

Novel iodinated carboranes: synthesis of the 8-iodo-7,9-dicarba-nido-undecaborate anion and 2-iodo-1,7-dicarba-closo-dodecaborane.

Electrophilic iodination of the 7,9-dicarba-nido-undecaborate anion with molecular iodine in the presence of AlCl3 generated a new carborane anion-8-iodo-7,9-dicarba-nido-undecaborate-in excellent yield. The capping of the new anion with HBCl2 yielded a previously unknown neutral iodinated carborane, 2-iodo-1,7-dicarba-closo-dodecaborane.

Diversification of EPR signatures in Site Directed Spin Labeling using a β-phosphorylated nitroxide.

Site Directed Spin Labeling (SDSL) combined with EPR spectroscopy is a very powerful approach to investigate structural transitions in proteins in particular flexible or even disordered ones. Conventional spin labels are based on nitroxide derivatives leading to classical 3-line spectra whose spectral shapes are indicative of the environment of the labels and thus constitute good reporters of structural modifications. However, the similarity of these spectral shapes precludes probing two regions of a protein or two partner proteins simultaneously.