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The mass spectrometry-based 'omics' sub-discipline that focuses on comprehensive, often exploratory, analyses of endogenous peptides involved in cell-to-cell communication is oftentimes referred to as peptidomics. Although the progress in bioanalytical technology development for peptide discovery has been tremendous, perhaps the largest advances have involved robust quantitative mass spectrometric approaches and data mining algorithms. These efforts have accelerated the discovery and validation of biomarkers, functionally important posttranslational modifications, and unexpected molecular interactions, information that aids drug development. In this article we outline the current approaches used in quantitative peptidomics and the technical challenges that stimulate new advances in the field, while also reviewing the newest literature on functional characterizations of endogenous peptides using quantitative mass spectrometry.
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http://dx.doi.org/10.1016/j.cbpa.2013.05.030 | DOI Listing |
J Pept Sci
October 2025
Institute of Technology, University of Tartu, Tartu, Estonia.
The development of therapeutic small interfering RNAs (siRNAs) has lately gained significant momentum due to their ability to silence genes in a highly specific manner. The main obstacle withholding the wider translation of siRNA-based drug modalities is their limited half-life and poor bioavailability, especially in extra-hepatic tissues. Consequently, various drug delivery systems (DDSs) have been developed to improve the delivery of siRNAs, including short delivery peptides called cell-penetrating peptides (CPPs).
View Article and Find Full Text PDFAnal Chim Acta
November 2025
Department of Chemical Engineering and Analytical Chemistry, Institute for Research on Nutrition and Food Safety (INSA·UB), University of Barcelona, Spain. Electronic address:
Background: Targeted bottom-up proteomics is of great interest for the straightforward, accurate, and sensitive measurement of specific protein biomarkers from surrogate peptide fragments. However, this approach typically relies on off-line enzymatic digestion with trypsin, a time-consuming step that may be inadequate for covering certain sequence regions containing important post-translational modifications (PTMs).
Results: In this study, we present an in-line enzymatic digestion strategy for the targeted bottom-up analysis of α-synuclein (α-syn), which is a protein biomarker of Parkinson's disease (PD).
Mol Pharmacol
August 2025
Department of Pharmacology, University of Michigan, Ann Arbor, Michigan.
μ-Opioid receptor (MOR) agonists are a mainstay in acute pain management. However, they also produce adverse effects and are frequently misused, increasing susceptibility for opioid use disorder. Thus, a strategy for improving the safety of opioid analgesics is needed.
View Article and Find Full Text PDFAgeing Res Rev
September 2025
Department of Pharmaceutical Toxicology, School of Pharmacy, China Medical University, Shenyang, 110122, China; Laboratory of Naturel Medicine for drug discovery, School of Pharmacy, China Medical University, Shenyang, 110122, China. Electronic address:
Calcium (Ca)/calmodulin (CaM)-dependent protein kinase II (CaMKII) is an emerging drug target for age-related diseases. It is a multifunctional kinase with complex activation modes, numerous isoforms, broad tissue distribution, and a dual role in health and disease. In particular, its isoforms share a high degree of conservation within the catalytic and regulatory domains, with only minor differences confined to the linker region.
View Article and Find Full Text PDFBiochem Pharmacol
September 2025
Section on Molecular Neuroscience, NIMH-IRP, Bethesda, MD, USA. Electronic address:
The PACAP receptor PAC1 is a G-coupled family B1 GPCR for which the highest-affinity endogenous peptide ligands are the pituitary adenylate cyclase-activating peptides PACAP38 and PACAP27, and whose most abundant endogenous ligand is PACAP38. PACAP action at PAC1 is implicated in neuropsychiatric disorders, atherosclerosis, pain chronification, and protection from neurodegeneration and ischemia. As PACAP also interacts with two related receptors, VPAC1 and VPAC2, highly selective ligands, both agonists and antagonists, for PAC1 have been sought.
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