Peptidomics: A Review of Clinical Applications and Methodologies

Abstract

Improvements in both liquid chromatography (LC) and mass spectrometry (MS) instrumentation have greatly enhanced proteomic and small molecule metabolomic analysis in recent years. Less focus has been on the improved capability to detect and quantify small bioactive peptides, even though the exact sequences of the peptide species produced can have important biological consequences. Endogenous bioactive peptide hormones, for example, are generated by the targeted and regulated cleavage of peptides from their prohormone sequence. This process may include organ specific variants, as proglucagon is converted to glucagon in the pancreas but glucagon-like peptide-1 (GLP-1) in the small intestine, with glucagon raising, whereas GLP-1, as an incretin, lowering blood glucose. Therefore, peptidomics workflows must preserve the structure of the processed peptide products to prevent the misidentification of ambiguous peptide species. The poor in vivo and in vitro stability of peptides in biological matrices is a major factor that needs to be considered when developing methods to study them. The bioinformatic analysis of peptidomics data sets requires the inclusion of specific posttranslational modifications, which are critical for the function of many bioactive peptides. This review aims to discuss and contrast the various extraction, analytical, and bioinformatics approaches used for human peptidomics studies in a multitude of matrices.

Ban-Lan-Gen Granule Alleviates Dextran Sulfate Sodium-Induced Chronic Relapsing Colitis in Mice via Regulating Gut Microbiota and Restoring Gut SCFA Derived-GLP-1 Production

“…Glucagon-like peptide-1 (GLP-1) is a cell type-specific post-translational product of proglucagon (Gcg) with antiinflammatory property. 28 As shown in Figure 7, DSS induced a significant decrease of Gcg mRNA expression in the colon compared with the control group, while BLG treatment could markedly reverse DSS-induced Gcg reduction (Figure 7A). In parallel, the level of GLP-1 in the serum was markedly decreased in the DSS-treated group, whereas BLG treatment could greatly prevent this decrease (Figure 7B).…”

On‐line reduction of insulin disulfide bonds with photoinduced radical reactions, upstream to nano liquid chromatography‐mass spectrometry

“…The most common separation principle utilized for peptide separations is RP‐LC [20], where organic solvents are strong eluates. To achieve compatibility between RP‐LC and inter‐chain cleavage with IPA/acetone solvent system, the amount of organic solvents needed to be reduced prior to the chromatographic system to avoid plug elution.…”

Clinical applications of plasma proteomics and peptidomics: Towards precision medicine

“…Relative to simple biochemical indicators, it can comprehensively evaluate the state of the disease as a whole, with higher stability and specificity. However, compared to the existing abundant plasma proteomics data, plasma peptidomics data is still limited [46, 138]. The fundamental reason for this is the high complexity of the plasma itself, coupled with the fact that endogenous plasma peptides are, as previously mentioned, typically present at relatively low abundance.…”