Advancing d-amino acid-containing peptide discovery in the metazoan

Mast, David H.; Checco, James W.; Sweedler, Jonathan V.

doi:10.1016/j.bbapap.2020.140553

Cited by 21 publications

(40 citation statements)

References 114 publications

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“…Despite this, stereoisomers are still overlooked in various tissues and/or physiological fluids, in peptide characterization experiments, and in the metabolomics process, thus demanding stereochemical analytical protocols [ 15 , 16 , 17 ].…”

Section: Chiral Metabolites and Lipids Separation By Liquid Chromatographymentioning

confidence: 99%

Enantioselectivity Effects in Clinical Metabolomics and Lipidomics

2021

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Metabolomics and lipidomics have demonstrated increasing importance in underlying biochemical mechanisms involved in the pathogenesis of diseases to identify novel drug targets and/or biomarkers for establishing therapeutic approaches for human health. Particularly, bioactive metabolites and lipids have biological activity and have been implicated in various biological processes in physiological conditions. Thus, comprehensive metabolites, and lipids profiling are required to obtain further advances in understanding pathophysiological changes that occur in cells and tissues. Chirality is one of the most important phenomena in living organisms and has attracted long-term interest in medical and natural science. Enantioselective separation plays a pivotal role in understanding the distribution and physiological function of a diversity of chiral bioactive molecules. In this context, it has been the goal of method development for targeted and untargeted metabolomics and lipidomic assays. Herein we will highlight the benefits and challenges involved in these stereoselective analyses for clinical samples.

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Section: Chiral Metabolites and Lipids Separation By Liquid Chromatographymentioning

confidence: 99%

Enantioselectivity Effects in Clinical Metabolomics and Lipidomics

2021

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“…D-Amino Acids (D-aa) in Nature D-aa are non-proteogenic, yet they have been found to occur in bioactive peptides in a wide variety of organisms [9], where their presence is important to increase their potency through the definition of specific conformations and increased resistance against enzymatic hydrolysis [10]. Their occurrence in metazoan organisms is well-documented, but it is anticipated that D-aa-containing peptides may have physiological effects within humans that are yet to be discovered [11]. In particular, D-Ser and D-Asp are the most abundant D-aa found in mammals, where they have physiological roles in neuromodulation and endocrine function [12].…”

Section: D-amino Acids (D-aa) In Naturementioning

confidence: 99%

“…Peptides with D-aa have been proposed for cancer therapy [21] as adhesive biomaterials [22], vaccine adjuvants [23], and as inhibitors of pathological amyloid fibrillization [24][25][26][27][28]. Furthermore, their occurrence in human peptides within the context of disease states has been detected thanks to sensitive, modern, analytical techniques (Figure 2) [11], and it has been proposed for biomarker detection strategies for diagnostics [29][30][31][32]. The detection of D-aa nevertheless remains a challenging task due to their lower occurrence relative to L-analogues in natural samples, for which workflow optimized protocols and new methods continue to emerge [33][34][35].…”

Section: D-amino Acids (D-aa) In Naturementioning

confidence: 99%

“…However, exactly predicting which type of turn is obtained is a different matter [36], one that is further complicated by the traditional turn assignment, based also on dihedral angles as those found on L-peptides [38], and their associated common conformations based on the Ramachandran plot [39,40]. It is worth noting that even a single amino acid isomerization from L-to D-can lead to quite different physicochemical properties [11]. One is increased hydrophobicity, which can be convenient to induce hydrophobically driven self-organization into nanostructured biomaterials, for instance [26,41,42].…”

Section: D-amino Acids (D-aa) In Naturementioning

confidence: 99%

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Polymer Conjugates of Antimicrobial Peptides (AMPs) with d-Amino Acids (d-aa): State of the Art and Future Opportunities

et al. 2022

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In recent years, antimicrobial peptides (AMPs) have enjoyed a renaissance, as the world is currently facing an emergency in terms of severe infections that evade antibiotics’ treatment. This is due to the increasing emergence and spread of resistance mechanisms. Covalent conjugation with polymers is an interesting strategy to modulate the pharmacokinetic profile of AMPs and enhance their biocompatibility profile. It can also be an effective approach to develop active coatings for medical implants and devices, and to avoid biofilm formation on their surface. In this concise review, we focus on the last 5 years’ progress in this area, pertaining in particular to AMPs that contain d-amino acids, as well as their role, and the advantages that may arise from their introduction into AMPs.

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“…The inversion of amino acid residue stereochemistry can manifest substantial alterations to the normal physiochemical or biological properties of endogenous peptides . Enzymatic l -to- d residue isomerization is an unusual post-translational modification (PTM) in the secretory pathway that contributes to the diversification of peptide structures and functions. , For decades, the products of l -to- d residue isomerization, d -amino acid containing peptides (DAACPs), have been isolated from numerous animal species; however, because the enzymes that catalyze isomerization are not known, conventional molecular biology or biochemistry approaches cannot be used to measure DAACPs in individual cells. As a result, peptide isomerization remains an underexplored PTM .…”

mentioning

confidence: 99%

Analysis of Peptide Stereochemistry in Single Cells by Capillary Electrophoresis–Trapped Ion Mobility Spectrometry Mass Spectrometry

et al. 2021

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Single cell analysis strives to probe molecular heterogeneity in morphologically similar cell populations through quantitative or qualitative measurements of genetic, proteomic, or metabolic products. Here, we applied mass analysis of single neurons to investigate cell–cell signaling peptides. The multiplicity of endogenous cell–cell signaling peptides is a common source of chemical diversity among cell populations. Certain peptides can undergo post-translational isomerization of select residues, which has important physiological consequences. The limited number of single cell analysis techniques that are sensitive to peptide stereochemistry make it challenging to study isomerization at the individual cell level. We performed capillary electrophoresis (CE) with mass spectrometry (MS) detection to characterize the peptide content of single cells. Using complementary trapped ion mobility spectrometry (TIMS) separations, we measured the stereochemical configurations of three neuropeptide gene products derived from the pleurin precursor in individual neurons (N = 3) isolated from the central nervous system of Aplysia californica. An analysis of the resultant mobility profiles indicated >98% of the detectable pleurin-derived peptides exist as the nonisomerized, all-l forms in individual neuron cell bodies. However, we observed 44% of the Plrn2 peptide from the pleurin precursor was present as the isomerized, d-residue-containing form in the nerve tissue. These findings demonstrate an unusual distribution of isomerized peptides in A. californica and establish CE–TIMS MS as a powerful analytical tool for investigating peptide stereochemistry at the single cell level.

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Advancing d-amino acid-containing peptide discovery in the metazoan

Cited by 21 publications

References 114 publications

Enantioselectivity Effects in Clinical Metabolomics and Lipidomics

Enantioselectivity Effects in Clinical Metabolomics and Lipidomics

Polymer Conjugates of Antimicrobial Peptides (AMPs) with d-Amino Acids (d-aa): State of the Art and Future Opportunities

Analysis of Peptide Stereochemistry in Single Cells by Capillary Electrophoresis–Trapped Ion Mobility Spectrometry Mass Spectrometry

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