LIVIVO - Search results -

Search results

Result 1 - 10 of total 50

Search options

Article ; Online: Identification of tyrosine sulfation in the variable region of a bispecific antibody and its effect on stability and biological activity.

Lietz, Christopher B / Deyanova, Ekaterina / Cho, Younhee / Cordia, Jon / Franc, Sarah / Kabro, Sally / Wang, Steven / Mikolon, David / Banks, Douglas D

mAbs

2023 Volume 15, Issue 1, Page(s) 2259289

Abstract: Despite tyrosine sulfation being a relatively common post-translational modification (PTM) on the secreted proteins of higher eukaryotic organisms, there have been surprisingly few reports of this modification occurring in recombinant monoclonal ... ...

Abstract	Despite tyrosine sulfation being a relatively common post-translational modification (PTM) on the secreted proteins of higher eukaryotic organisms, there have been surprisingly few reports of this modification occurring in recombinant monoclonal antibodies (mAbs) expressed by mammalian cell lines and even less information regarding its potential impact on mAb efficacy and stability. This discrepancy is likely due to the extreme lability of this modification using many of the mass spectrometry methods typically used within the biopharmaceutical industry for PTM identification, as well as the possible misidentification as phosphorylation. Here, we identified sulfation on a single tyrosine residue located within the identical variable region sequence of a 2 + 1 bispecific mAbs heavy and heavy-heavy chains using a multi-enzymatic approach in combination with mass spectrometry analysis and examined its impact on binding, efficacy, and physical stability. Unlike previous reports, we found that tyrosine sulfation modestly decreased the mAb cell binding and T cell-mediated killing, primarily by increasing the rate of antigen disassociation as determined from surface plasmon resonance-binding experiments. We also found that, while this acidic modification had no significant impact on the mAb thermal stability, sulfation did modestly increase its rate of aggregation, presumably by lowering the mAb's colloidal stability as indicated by polyethylene glycol induced liquid-liquid phase separation experiments.
MeSH term(s)	Animals ; Tyrosine/chemistry ; Recombinant Proteins/metabolism ; Mass Spectrometry ; Antibodies, Monoclonal/chemistry ; Cell Line ; Antibodies, Bispecific ; Mammals/metabolism
Chemical Substances	Tyrosine (42HK56048U) ; Recombinant Proteins ; Antibodies, Monoclonal ; Antibodies, Bispecific
Language	English
Publishing date	2023-09-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	2537838-7
ISSN	1942-0870 ; 1942-0870
ISSN (online)	1942-0870
ISSN	1942-0870
DOI	10.1080/19420862.2023.2259289
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Article ; Online: Human iN neuronal model of schizophrenia displays dysregulation of chromogranin B and related neuropeptide transmitter signatures.

Podvin, Sonia / Jones, Jeffrey / Kang, Austin / Goodman, Ryan / Reed, Patrick / Lietz, Christopher B / Then, Joshua / Lee, Kelly C / Eyler, Lisa T / Jeste, Dilip V / Gage, Fred H / Hook, Vivian

Molecular psychiatry

2024

Abstract: Schizophrenia (SZ) is a serious mental illness and neuropsychiatric brain disorder with behavioral symptoms that include hallucinations, delusions, disorganized behavior, and cognitive impairment. Regulation of such behaviors requires utilization of ... ...

Abstract	Schizophrenia (SZ) is a serious mental illness and neuropsychiatric brain disorder with behavioral symptoms that include hallucinations, delusions, disorganized behavior, and cognitive impairment. Regulation of such behaviors requires utilization of neurotransmitters released to mediate cell-cell communication which are essential to brain functions in health and disease. We hypothesized that SZ may involve dysregulation of neurotransmitters secreted from neurons. To gain an understanding of human SZ, induced neurons (iNs) were derived from SZ patients and healthy control subjects to investigate peptide neurotransmitters, known as neuropeptides, which represent the major class of transmitters. The iNs were subjected to depolarization by high KCl in the culture medium and the secreted neuropeptides were identified and quantitated by nano-LC-MS/MS tandem mass spectrometry. Several neuropeptides were identified from schizophrenia patient-derived neurons, including chromogranin B (CHGB), neurotensin, and natriuretic peptide. Focusing on the main secreted CHGB neuropeptides, results revealed differences in SZ iNs compared to control iN neurons. Lower numbers of distinct CHGB peptides were found in the SZ secretion media compared to controls. Mapping of the peptides to the CHGB precursor revealed peptides unique to either SZ or control, and peptides common to both conditions. Also, the iNs secreted neuropeptides under both KCl and basal (no KCl) conditions. These findings are consistent with reports that chromogranin B levels are reduced in the cerebrospinal fluid and specific brain regions of SZ patients. These findings suggest that iNs derived from SZ patients can model the decreased CHGB neuropeptides observed in human SZ.
Language	English
Publishing date	2024-02-02
Publishing country	England
Document type	Journal Article
ZDB-ID	1330655-8
ISSN	1476-5578 ; 1359-4184
ISSN (online)	1476-5578
ISSN	1359-4184
DOI	10.1038/s41380-024-02422-x
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 4812: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article: Coupling matrix-assisted ionization with high resolution mass spectrometry and electron transfer dissociation to characterize intact proteins and post-translational modifications

Chen, Bingming / Lietz, ChristopherB / Li, Lingjun

Analytical and bioanalytical chemistry. 2018 Jan., v. 410, no. 3

2018

Abstract: Matrix-assisted ionization (MAI) is a recently developed ionization technique that produces multiply charged ions on either electrospray ionization (ESI) or matrix-assisted laser desorption/ionization (MALDI) platform without the need of high voltage or ... ...

Abstract	Matrix-assisted ionization (MAI) is a recently developed ionization technique that produces multiply charged ions on either electrospray ionization (ESI) or matrix-assisted laser desorption/ionization (MALDI) platform without the need of high voltage or laser ablation. In this study, MAI has been coupled to a high resolution accurate mass (HRAM) hybrid instrument, the Orbitrap Elite mass spectrometer, with electron transfer dissociation (ETD) module for fast peptide and intact protein characterization. The softness of MAI process preserves labile post-translational modifications (PTM) and allows fragmentation and localization by ETD. Moreover, MAI on ESI platform allows rapid sample preparation and analysis (~ 1 min/sample) due to the easiness of sample introduction. It significantly improves the throughput compared to ESI direct infusion and MAI on MALDI platform, which usually takes more than 10 min/sample. Intact protein standards, protein mixtures, and neural tissue extracts have been characterized using this instrument platform with both full MS and MS/MS (CID, HCD, and ETD) analyses. Furthermore, the performances of ESI, MALDI, and MAI on both platforms have been tested to provide a systematic comparison among these techniques. With improved ETD performance and PTM analysis capabilities, we anticipate that the HRAM MAI-MS with ETD module will offer greater utilities in large molecule characterization with enhanced speed and coverage. These advancements will enable promising applications in bottom-up and top-down protein analyses. Graphical abstract Matrix-assisted ionization (MAI) for characterizing intact proteins and post-translational modifications with representative mass spectra from intact proteins.
Keywords	dissociation ; electric power ; electron transfer ; hardness ; ionization ; ions ; mass spectrometry ; post-translational modification ; proteins ; spectrometers
Language	English
Dates of publication	2018-01
Size	p. 1007-1017.
Publishing place	Springer Berlin Heidelberg
Document type	Article
ISSN	1618-2642
DOI	10.1007/s00216-017-0611-4
Database	NAL-Catalogue (AGRICOLA)

Full text online

Accessible to users with ZB MED library card

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Details ▾
- Full text online
- Order with fees

Article ; Online: Coupling matrix-assisted ionization with high resolution mass spectrometry and electron transfer dissociation to characterize intact proteins and post-translational modifications.

Chen, Bingming / Lietz, Christopher B / Li, Lingjun

Analytical and bioanalytical chemistry

2017 Volume 410, Issue 3, Page(s) 1007–1017

Abstract	Matrix-assisted ionization (MAI) is a recently developed ionization technique that produces multiply charged ions on either electrospray ionization (ESI) or matrix-assisted laser desorption/ionization (MALDI) platform without the need of high voltage or laser ablation. In this study, MAI has been coupled to a high resolution accurate mass (HRAM) hybrid instrument, the Orbitrap Elite mass spectrometer, with electron transfer dissociation (ETD) module for fast peptide and intact protein characterization. The softness of MAI process preserves labile post-translational modifications (PTM) and allows fragmentation and localization by ETD. Moreover, MAI on ESI platform allows rapid sample preparation and analysis (~ 1 min/sample) due to the easiness of sample introduction. It significantly improves the throughput compared to ESI direct infusion and MAI on MALDI platform, which usually takes more than 10 min/sample. Intact protein standards, protein mixtures, and neural tissue extracts have been characterized using this instrument platform with both full MS and MS/MS (CID, HCD, and ETD) analyses. Furthermore, the performances of ESI, MALDI, and MAI on both platforms have been tested to provide a systematic comparison among these techniques. With improved ETD performance and PTM analysis capabilities, we anticipate that the HRAM MAI-MS with ETD module will offer greater utilities in large molecule characterization with enhanced speed and coverage. These advancements will enable promising applications in bottom-up and top-down protein analyses. Graphical abstract Matrix-assisted ionization (MAI) for characterizing intact proteins and post-translational modifications with representative mass spectra from intact proteins.
MeSH term(s)	Amino Acid Sequence ; Animals ; Electron Transport ; Equipment Design ; Female ; Glycopeptides/analysis ; Phosphopeptides/analysis ; Protein Processing, Post-Translational ; Proteins/chemistry ; Rats, Sprague-Dawley ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/instrumentation ; Tandem Mass Spectrometry/instrumentation
Chemical Substances	Glycopeptides ; Phosphopeptides ; Proteins
Language	English
Publishing date	2017-09-12
Publishing country	Germany
Document type	Journal Article
ZDB-ID	201093-8
ISSN	1618-2650 ; 0016-1152 ; 0372-7920
ISSN (online)	1618-2650
ISSN	0016-1152 ; 0372-7920
DOI	10.1007/s00216-017-0611-4
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Bonn / Germany

Z 4' 69/97: Show issues
Archiv 3: Show issues
Z 9.4: Show issues

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Details ▾

Article ; Online: Highly multiplexed quantitative proteomic and phosphoproteomic analyses in vascular smooth muscle cell dedifferentiation.

Zhong, Xiaofang / Lietz, Christopher B / Shi, Xudong / Buchberger, Amanda R / Frost, Dustin C / Li, Lingjun

Analytica chimica acta

2020 Volume 1127, Page(s) 163–173

Abstract: Restenosis, re-narrowing of arterial lumen following intervention for cardiovascular disease, remains a major issue limiting the long-term therapeutic efficacy of treatment. The signaling molecules, TGFβ (transforming growth factor-beta) and Smad3, play ... ...

Abstract	Restenosis, re-narrowing of arterial lumen following intervention for cardiovascular disease, remains a major issue limiting the long-term therapeutic efficacy of treatment. The signaling molecules, TGFβ (transforming growth factor-beta) and Smad3, play important roles in vascular restenosis, but very little is yet known about the down-stream dynamics in global protein expression and phosphorylation. Here, we develop a highly multiplexed quantitative proteomic and phosphoproteomic strategy employing 12-plex N,N-dimethyl leucine (DiLeu) isobaric tags and The DiLeu Tool software to globally assess protein expression and phosphorylation changes in smooth muscle cells (SMCs) treated with TGFβ/Smad3 and/or SDF-1α (stromal cell-derived factor). A total of 4086 proteins were quantified in the combined dataset of proteome and phosphoproteome across 12-plex DiLeu-labeled SMC samples. 2317 localized phosphorylation sites were quantified, corresponding to 1193 phosphoproteins. TGFβ/Smad3 induced up-regulation of 40 phosphosites and down-regulation of 50 phosphosites, and TGFβ/Smad3-specific SDF-1α exclusively facilitated up-regulation of 27 phosphosites and down-regulation of 47 phosphosites. TGFβ/Smad3 inhibited the expression of contractile-associated proteins including smooth muscle myosin heavy chain, calponin, cardiac muscle alpha-actin, and smooth muscle protein 22α. Gene ontology and pathway enrichment analysis revealed that elevated TGFβ/Smad3 activated cell proliferation and TGFβ signaling pathway, sequentially stimulating phosphorylation of CXCR4 (C-X-C chemokine receptor 4). SDF-1α/CXCR4 activated extracellular signal-regulating kinase signaling pathway and facilitated the expression of synthetic marker, osteopontin, which was validated through targeted analysis. These findings provide new insights into the mechanisms of TGFβ regulated SMC dedifferentiation, as well as new avenues for designing effective therapeutics for vascular disease.
MeSH term(s)	Cell Dedifferentiation ; Muscle, Smooth, Vascular ; Myocytes, Smooth Muscle ; Proteomics ; Transforming Growth Factor beta
Chemical Substances	Transforming Growth Factor beta
Language	English
Publishing date	2020-07-08
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1483436-4
ISSN	1873-4324 ; 0003-2670
ISSN (online)	1873-4324
ISSN	0003-2670
DOI	10.1016/j.aca.2020.06.054
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

Order via subito

Details ▾
- Full text online
- Order with fees

Article ; Online: Proteomic Modulation in the Dorsal Spinal Cord Following Spinal Cord Stimulation Therapy in an In Vivo Neuropathic Pain Model.

Tilley, Dana M / Lietz, Christopher B / Cedeno, David L / Kelley, Courtney A / Li, Lingjun / Vallejo, Ricardo

Neuromodulation : journal of the International Neuromodulation Society

2020 Volume 24, Issue 1, Page(s) 22–32

Abstract: Objectives: Spinal cord stimulation (SCS) provides relief for patients suffering from chronic neuropathic pain although its mechanism may not be as dependent on electrical interference as classically considered. Recent evidence has been growing ... ...

Abstract	Objectives: Spinal cord stimulation (SCS) provides relief for patients suffering from chronic neuropathic pain although its mechanism may not be as dependent on electrical interference as classically considered. Recent evidence has been growing regarding molecular changes that are induced by SCS as being a key player in reversing the pain process. Here, we observed the effect of SCS on altering protein expression in spinal cord tissue using a proteomic analysis approach. Methods: A microlead was epidurally implanted following induction of an animal neuropathic pain model. After the model was established, stimulation was applied for 72 hours continuously followed by tissue collection and proteomic analysis via tandem mass spectroscopy. Identified proteins were run through online data bases for protein identification and classification of biological processes. Results: A significant improvement in mechanical sensitivity was observed following 48 hours of SCS therapy. Proteomic analysis identified 5840 proteins, of which 155 were significantly affected by SCS. Gene ontology data bases indicated that a significant number of proteins were associated to stress response, oxidation/reduction, or extracellular matrix pathways. Additionally, many of the proteins identified also play a role in neuron-glial interactions and are involved in nociception. Conclusions: The development of an injury unbalances the proteome of the local neural tissue, neurons, and glial cells, and shifts the proteomic profile to a pain producing state. This study demonstrates the reversal of the injury-induced proteomic state by applying conventional SCS therapy. Additional studies looking at variations in electrical parameters are needed to optimize SCS.
MeSH term(s)	Animals ; Disease Models, Animal ; Humans ; Neuralgia/etiology ; Neuralgia/therapy ; Proteomics ; Spinal Cord ; Spinal Cord Stimulation
Language	English
Publishing date	2020-03-10
Publishing country	United States
Document type	Journal Article
ZDB-ID	1500372-3
ISSN	1525-1403 ; 1094-7159
ISSN (online)	1525-1403
ISSN	1094-7159
DOI	10.1111/ner.13103
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 5912: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾

Article ; Online: Differential Neuropeptidomes of Dense Core Secretory Vesicles (DCSV) Produced at Intravesicular and Extracellular pH Conditions by Proteolytic Processing.

Jiang, Zhenze / Lietz, Christopher B / Podvin, Sonia / Yoon, Michael C / Toneff, Thomas / Hook, Vivian / O'Donoghue, Anthony J

ACS chemical neuroscience

2021 Volume 12, Issue 13, Page(s) 2385–2398

Abstract: Neuropeptides mediate cell-cell signaling in the nervous and endocrine systems. The neuropeptidome is the spectrum of peptides generated from precursors by proteolysis within dense core secretory vesicles (DCSV). DCSV neuropeptides and contents are ... ...

Abstract	Neuropeptides mediate cell-cell signaling in the nervous and endocrine systems. The neuropeptidome is the spectrum of peptides generated from precursors by proteolysis within dense core secretory vesicles (DCSV). DCSV neuropeptides and contents are released to the extracellular environment where further processing for neuropeptide formation may occur. To assess the DCSV proteolytic capacity for production of neuropeptidomes at intravesicular pH 5.5 and extracellular pH 7.2, neuropeptidomics, proteomics, and protease assays were conducted using chromaffin granules (CG) purified from adrenal medulla. CG are an established model of DCSV. The CG neuropeptidome consisted of 1239 unique peptides derived from 15 proneuropeptides that were colocalized with 64 proteases. Distinct CG neuropeptidomes were generated at the internal DCSV pH of 5.5 compared to the extracellular pH of 7.2. Class-specific protease inhibitors differentially regulated neuropeptidome production involving aspartic, cysteine, serine, and metallo proteases. The substrate cleavage properties of CG proteases were assessed by multiplex substrate profiling by mass spectrometry (MSP-MS) that uses a synthetic peptide library containing diverse cleavage sites for endopeptidases and exopeptidases. Parallel inhibitor-sensitive cleavages for neuropeptidome production and peptide library proteolysis led to elucidation of six CG proteases involved in neuropeptidome production, represented by cathepsins A, B, C, D, and L and carboxypeptidase E (CPE). The MSP-MS profiles of these six enzymes represented the majority of CG proteolytic cleavages utilized for neuropeptidome production. These findings provide new insight into the DCSV proteolytic system for production of distinct neuropeptidomes at the internal CG pH of 5.5 and at the extracellular pH of 7.2.
MeSH term(s)	Adrenal Medulla ; Amino Acid Sequence ; Hydrogen-Ion Concentration ; Proteolysis ; Secretory Vesicles/metabolism
Language	English
Publishing date	2021-06-21
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1948-7193
ISSN (online)	1948-7193
DOI	10.1021/acschemneuro.1c00133
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article: In Depth Quantification of Extracellular Matrix Proteins from Human Pancreas

Ma, Fengfei / Tremmel, Daniel M / Li, Zihui / Lietz, Christopher B / Sackett, Sara Dutton / Odorico, Jon S / Li, Lingjun

Journal of proteome research. 2019 June 14, v. 18, no. 8

2019

Abstract: Extracellular matrix (ECM) is an important component of the pancreatic microenvironment which regulates β cell proliferation, differentiation, and insulin secretion. Protocols have recently been developed for the decellularization of the human pancreas ... ...

Abstract	Extracellular matrix (ECM) is an important component of the pancreatic microenvironment which regulates β cell proliferation, differentiation, and insulin secretion. Protocols have recently been developed for the decellularization of the human pancreas to generate functional scaffolds and hydrogels. In this work, we characterized human pancreatic ECM composition before and after decellularization using isobaric dimethylated leucine (DiLeu) labeling for relative quantification of ECM proteins. A novel correction factor was employed in the study to eliminate the bias introduced during sample preparation. In comparison to the commonly employed sample preparation methods (urea and FASP) for proteomic analysis, a recently developed surfactant and chaotropic agent assisted sequential extraction/on pellet digestion (SCAD) protocol has provided an improved strategy for ECM protein extraction of human pancreatic ECM matrix. The quantitative proteomic results revealed the preservation of matrisome proteins while most of the cellular proteins were removed. This method was compared with a well-established label-free quantification (LFQ) approach which rendered similar expressions of different categories of proteins (collagens, ECM glycoproteins, proteoglycans, etc.). The distinct expression of ECM proteins was quantified comparing adult and fetal pancreas ECM, shedding light on the correlation between matrix composition and postnatal β cell maturation. Despite the distinct profiles of different subcategories in the native pancreas, the distribution of matrisome proteins exhibited similar trends after the decellularization process. Our method generated a large data set of matrisome proteins from a single tissue type. These results provide valuable insight into the possibilities of constructing a bioengineered pancreas. It may also facilitate better understanding of the potential roles that matrisome proteins play in postnatal β cell maturation.
Keywords	adults ; cell proliferation ; data collection ; extracellular matrix ; extracellular matrix proteins ; humans ; hydrogels ; insulin secretion ; leucine ; pancreas ; proteoglycans ; proteolysis ; proteome ; proteomics ; surfactants ; urea
Language	English
Dates of publication	2019-0614
Size	p. 3156-3165.
Publishing place	American Chemical Society
Document type	Article
ZDB-ID	2078618-9
ISSN	1535-3907 ; 1535-3893
ISSN (online)	1535-3907
ISSN	1535-3893
DOI	10.1021/acs.jproteome.9b00241
Database	NAL-Catalogue (AGRICOLA)

In stock of ZB MED Cologne/Königswinter

Zs.A 6189: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Diversity of Neuropeptide Cell-Cell Signaling Molecules Generated by Proteolytic Processing Revealed by Neuropeptidomics Mass Spectrometry.

Hook, Vivian / Lietz, Christopher B / Podvin, Sonia / Cajka, Tomas / Fiehn, Oliver

Journal of the American Society for Mass Spectrometry

2018 Volume 29, Issue 5, Page(s) 807–816

Abstract: Neuropeptides are short peptides in the range of 3-40 residues that are secreted for cell-cell communication in neuroendocrine systems. In the nervous system, neuropeptides comprise the largest group of neurotransmitters. In the endocrine system, ... ...

Abstract	Neuropeptides are short peptides in the range of 3-40 residues that are secreted for cell-cell communication in neuroendocrine systems. In the nervous system, neuropeptides comprise the largest group of neurotransmitters. In the endocrine system, neuropeptides function as peptide hormones to coordinate intercellular signaling among target physiological systems. The diversity of neuropeptide functions is defined by their distinct primary sequences, peptide lengths, proteolytic processing of pro-neuropeptide precursors, and covalent modifications. Global, untargeted neuropeptidomics mass spectrometry is advantageous for defining the structural features of the thousands to tens of thousands of neuropeptides present in biological systems. Defining neuropeptide structures is the basis for defining the proteolytic processing pathways that convert pro-neuropeptides into active peptides. Neuropeptidomics has revealed that processing of pro-neuropeptides occurs at paired basic residues sites, and at non-basic residue sites. Processing results in neuropeptides with known functions and generates novel peptides representing intervening peptide domains flanked by dibasic residue processing sites, identified by neuropeptidomics. While very short peptide products of 2-4 residues are predicted from pro-neuropeptide dibasic processing sites, such peptides have not been readily identified; therefore, it will be logical to utilize metabolomics to identify very short peptides with neuropeptidomics in future studies. Proteolytic processing is accompanied by covalent post-translational modifications (PTMs) of neuropeptides comprising C-terminal amidation, N-terminal pyroglutamate, disulfide bonds, phosphorylation, sulfation, acetylation, glycosylation, and others. Neuropeptidomics can define PTM features of neuropeptides. In summary, neuropeptidomics for untargeted, global analyses of neuropeptides is essential for elucidation of proteases that generate diverse neuropeptides for cell-cell signaling. Graphical Abstract ᅟ.
MeSH term(s)	Amino Acid Sequence ; Animals ; Biosynthetic Pathways ; Brain/metabolism ; Brain Chemistry ; Cell Communication ; Humans ; Mass Spectrometry/methods ; Metabolomics/methods ; Neuropeptides/analysis ; Neuropeptides/metabolism ; Protein Processing, Post-Translational ; Proteolysis ; Proteomics/methods
Chemical Substances	Neuropeptides
Language	English
Publishing date	2018-04-17
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1073671-2
ISSN	1879-1123 ; 1044-0305
ISSN (online)	1879-1123
ISSN	1044-0305
DOI	10.1007/s13361-018-1914-1
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 4618: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 241: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Phosphopeptidomics Reveals Differential Phosphorylation States and Novel SxE Phosphosite Motifs of Neuropeptides in Dense Core Secretory Vesicles.

Lietz, Christopher B / Toneff, Thomas / Mosier, Charles / Podvin, Sonia / O'Donoghue, Anthony J / Hook, Vivian

Journal of the American Society for Mass Spectrometry

2018 Volume 29, Issue 5, Page(s) 935–947

Abstract: Neuropeptides are vital for cell-cell communication and function in the regulation of the nervous and endocrine systems. They are generated by post-translational modification (PTM) steps resulting in small active peptides generated from prohormone ... ...

Abstract	Neuropeptides are vital for cell-cell communication and function in the regulation of the nervous and endocrine systems. They are generated by post-translational modification (PTM) steps resulting in small active peptides generated from prohormone precursors. Phosphorylation is a significant PTM for the bioactivity of neuropeptides. From the known diversity of distinct neuropeptide functions, it is hypothesized that the extent of phosphorylation varies among different neuropeptides. To assess this hypothesis, neuropeptide-containing dense core secretory vesicles from bovine adrenal medullary chromaffin cells were subjected to global phosphopeptidomics analyses by liquid chromatography (LC)-mass spectrometry (MS/MS). Phosphopeptides were identified directly by LC-MS/MS and indirectly by phosphatase treatment followed by LC-MS/MS. The data identified numerous phosphorylated peptides derived from neuropeptide precursors such as chromogranins, secretogranins, proenkephalin and pro-NPY. Phosphosite occupancies were observed at high and low levels among identified peptides and many of the high occupancy phosphopeptides represent prohormone-derived peptides with currently unknown bioactivities. Peptide sequence analyses demonstrated SxE as the most prevalent phosphorylation site motif, corresponding to phosphorylation sites of the Fam20C protein kinase known to be present in the secretory pathway. The range of high to low phosphosite occupancies for neuropeptides demonstrates cellular regulation of neuropeptide phosphorylation. Graphical Abstract ᅟ.
MeSH term(s)	Adrenal Glands/chemistry ; Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Cattle ; Neuropeptides/analysis ; Phosphopeptides/analysis ; Phosphorylation ; Protein Processing, Post-Translational ; Secretory Vesicles/chemistry ; Tandem Mass Spectrometry
Chemical Substances	Neuropeptides ; Phosphopeptides
Language	English
Publishing date	2018-03-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	1073671-2
ISSN	1879-1123 ; 1044-0305
ISSN (online)	1879-1123
ISSN	1044-0305
DOI	10.1007/s13361-018-1915-0
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 4618: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 241: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

To top

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

Full text online

More links

Kategorien

In stock of ZB MED Bonn / Germany

Order via subito

Inter-library loan at ZB MED

Full text online

More links

Kategorien

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito