Publications by authors named "R Melani"
Multiplexed proteomics has become a powerful tool for investigating biological systems. Using balancer-peptide conjugates (e.g.
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- - Cirrhosis affects 2 to 5 million Americans, with most patients experiencing compensated cirrhosis, yet many can develop serious complications that severely shorten life expectancy.
- - Identifying high-risk patients with compensated cirrhosis is crucial for improving their care and directing them to specialty treatment, as not all patients receive this level of care.
- - This pilot study identified 209 differentially expressed proteoforms in the plasma of cirrhosis patients at various stages, highlighting potential biomarkers that could help in early diagnosis and risk assessment.
Article Synopsis
- Antibody-drug conjugates (ADCs) are a new type of treatment that merge the effectiveness of toxic drugs with the precision of antibodies, but their complex structure makes analysis challenging.
- The use of middle-down mass spectrometry (MD MS) faces issues with spectral congestion, which can hide important fragment ions that reveal drug attachment sites.
- Proton transfer charge reduction (PTCR) is introduced to simplify these spectra, allowing for a more effective investigation of ADCs and improving the identification of drug localization compared to traditional methods.
Modern mass spectrometry technology allows for extensive sequencing of the ~ 25 kDa subunits of monoclonal antibodies (mAbs) produced by IdeS proteolysis followed by disulfide bond reduction, an approach known as middle-down mass spectrometry (MD MS). However, the spectral congestion of tandem mass spectra of large polypeptides dramatically complicates fragment ion assignment. Here, we report the development and benchmark of an MD MS strategy based on the combination of different ion fragmentation techniques with proton transfer charge reduction (PTCR) to simplify the gas-phase sequencing of mAb subunits.
View Article and Find Full Text PDFHost cell proteins (HCPs) are one of the process-related impurities that need to be well characterized and controlled throughout biomanufacturing processes to assure the quality, safety, and efficacy of monoclonal antibodies (mAbs) and other protein-based biopharmaceuticals. Although ELISA remains the gold standard method for quantification of total HCPs, it lacks the specificity and coverage to identify and quantify individual HCPs. As a complementary method to ELISA, the LC-MS/MS method has emerged as a powerful tool to identify and profile individual HCPs during the downstream purification process.
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