{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/97668"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/97668","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Analysis of D-amino acid-containing neuropeptides in mollusks and rodents","abstract":"Modern mass spectrometry (MS)-based neuropeptidomics continues to reveal an unprecedented level of chemical complexity in the nervous system on the peptide level, with sometimes hundreds of peptides expressed by or secreted onto specific structures. These neuropeptides have evolved for animal behaviors and regulating neuronal circuits. Neuropeptides exert their responses through GPCRs in most cases, and in order to interact with the GPCR, their structure is important. Their structures are not solely defined by their peptide sequence, but may instead depend on the myriad post-translational modifications (PTMs) they undergo. Thus, the hunt for neuropeptides must include the discovery of the exact chemical forms of the physiologically active peptides as these are required to achieve their receptor binding capability, degradation and uptake pathways, and hence bioactivity. Life, on a molecular level, has a stereoselective preference for many biochemical processes. This is especially true for protein-derived neuropeptides, which are translated by ribosomes using exclusively L-amino acids. However, D-amino acids are present in animal peptides, first evidenced by dermorphin, an analgesic skin peptide in Phyllomedusa sauvagei. Dermorphin’s existence as a D-amino acid-containing peptide (DAACP) proved not to be a singularity, but instead revealed a novel post-translational modification: peptide isomerization. Roughly 40 endogenous animal DAACPs have been found in 3 evolutionarily distinct phyla as toxins, hormones, and importantly for this work, neuropeptides. Isomerization alters the three-dimensional shape of a peptide. This change in shape has been associated with a change in bioactivity of a peptide, with the DAACP being the sole bioactive form. However, isomerization does not change the molecular weight of a peptide, making it difficult to detect using MS. Thus, bioactive peptides are likely hiding in neuropeptidomics study under the assumption that these peptides, like the majority of life, are formed solely of L-amino acids. Understanding the physiological purpose of DAACPs requires their further discovery. An approach to characterize unknown DAACPs, the DAACP discovery funnel, is presented in this work. It aims to solve this problem through a series of adapted MS-based analytical techniques capable of identifying potential DAACPs and assaying their amino acids for their chiral state. The discovery funnel is used to discover new DAACPs in the Aplysia californica nervous system and is applied, as pioneering work, to nervous system structures in rodents.","abstract_html":"Modern mass spectrometry (MS)-based neuropeptidomics continues to reveal an unprecedented level of chemical complexity in the nervous system on the peptide level, with sometimes hundreds of peptides expressed by or secreted onto specific structures. These neuropeptides have evolved for animal behaviors and regulating neuronal circuits. Neuropeptides exert their responses through GPCRs in most cases, and in order to interact with the GPCR, their structure is important. Their structures are not solely defined by their peptide sequence, but may instead depend on the myriad post-translational modifications (PTMs) they undergo. Thus, the hunt for neuropeptides must include the discovery of the exact chemical forms of the physiologically active peptides as these are required to achieve their receptor binding capability, degradation and uptake pathways, and hence bioactivity. Life, on a molecular level, has a stereoselective preference for many biochemical processes. This is especially true for protein-derived neuropeptides, which are translated by ribosomes using exclusively L-amino acids. However, D-amino acids are present in animal peptides, first evidenced by dermorphin, an analgesic skin peptide in Phyllomedusa sauvagei. Dermorphin’s existence as a D-amino acid-containing peptide (DAACP) proved not to be a singularity, but instead revealed a novel post-translational modification: peptide isomerization. Roughly 40 endogenous animal DAACPs have been found in 3 evolutionarily distinct phyla as toxins, hormones, and importantly for this work, neuropeptides. Isomerization alters the three-dimensional shape of a peptide. This change in shape has been associated with a change in bioactivity of a peptide, with the DAACP being the sole bioactive form. However, isomerization does not change the molecular weight of a peptide, making it difficult to detect using MS. Thus, bioactive peptides are likely hiding in neuropeptidomics study under the assumption that these peptides, like the majority of life, are formed solely of L-amino acids. Understanding the physiological purpose of DAACPs requires their further discovery. An approach to characterize unknown DAACPs, the DAACP discovery funnel, is presented in this work. It aims to solve this problem through a series of adapted MS-based analytical techniques capable of identifying potential DAACPs and assaying their amino acids for their chiral state. The discovery funnel is used to discover new DAACPs in the Aplysia californica nervous system and is applied, as pioneering work, to nervous system structures in rodents.","abstract_has_math":false,"creators":["Livnat, Itamar"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Molecular & Integrative Physi","degree_department":null,"school":null,"contributors":["Sweedler, Jonathan V.","Gillette, Martha U.","Raetzman, Lori T.","Rhodes, Justin S."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2017,"date_issued":"2017-08-10T20:32:41Z","date_published":"2017-08-10T20:32:41Z","updated_at":"2026-07-22T22:24:34Z","subjects":["Neurochemistry","D-amino acid-containing peptides","Neuropeptides","Mass spectrometry (MS)","Liquid chromatography","Aplysia californica","Liquid chromatography–mass spectrometry (LC-MS)","Liquid chromatography–mass spectrometry/mass spectrometry (LC-MS/MS)"],"languages":["en"],"rights":["Copyright 2016 Itamar Livnat"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/2142/97668","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Sweedler, Jonathan V.","Gillette, Martha U.","Raetzman, Lori T.","Rhodes, Justin S."]},{"key":"dc:creator","label":"Author","values":["Livnat, Itamar"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2017-08-10T20:32:41Z","2019-08-11T09:15:35Z","2017-04-03","2017-05"]},{"key":"dc:type","label":"Dc Type","values":["text"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Molecular & Integrative Physi"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Illinois at Urbana-Champaign"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Neurochemistry","D-amino acid-containing peptides","Neuropeptides","Mass spectrometry (MS)","Liquid chromatography","Aplysia californica","Liquid chromatography–mass spectrometry (LC-MS)","Liquid chromatography–mass spectrometry/mass spectrometry (LC-MS/MS)"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright 2016 Itamar Livnat"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/2142/97668"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Modern mass spectrometry (MS)-based neuropeptidomics continues to reveal an unprecedented level of chemical complexity in the nervous system on the peptide level, with sometimes hundreds of peptides expressed by or secreted onto specific structures. 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Dermorphin’s existence as a D-amino acid-containing peptide (DAACP) proved not to be a singularity, but instead revealed a novel post-translational modification: peptide isomerization. Roughly 40 endogenous animal DAACPs have been found in 3 evolutionarily distinct phyla as toxins, hormones, and importantly for this work, neuropeptides. Isomerization alters the three-dimensional shape of a peptide. This change in shape has been associated with a change in bioactivity of a peptide, with the DAACP being the sole bioactive form. However, isomerization does not change the molecular weight of a peptide, making it difficult to detect using MS. Thus, bioactive peptides are likely hiding in neuropeptidomics study under the assumption that these peptides, like the majority of life, are formed solely of L-amino acids. Understanding the physiological purpose of DAACPs requires their further discovery. An approach to characterize unknown DAACPs, the DAACP discovery funnel, is presented in this work. It aims to solve this problem through a series of adapted MS-based analytical techniques capable of identifying potential DAACPs and assaying their amino acids for their chiral state. The discovery funnel is used to discover new DAACPs in the Aplysia californica nervous system and is applied, as pioneering work, to nervous system structures in rodents.","Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2019-05-01","The student, Itamar Livnat, accepted the attached license on 2017-04-02 at 23:57.","The student, Itamar Livnat, submitted this Dissertation for approval on 2017-04-03 at 00:08.","This Dissertation was approved for publication on 2017-04-03 at 11:36.","DSpace SAF Submission Ingestion Package generated from Vireo submission #10617 on 2017-08-10 at 15:05:02","Made available in DSpace on 2017-08-10T20:32:41Z (GMT). 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Dermorphin’s existence as a D-amino acid-containing peptide (DAACP) proved not to be a singularity, but instead revealed a novel post-translational modification: peptide isomerization. Roughly 40 endogenous animal DAACPs have been found in 3 evolutionarily distinct phyla as toxins, hormones, and importantly for this work, neuropeptides. Isomerization alters the three-dimensional shape of a peptide. This change in shape has been associated with a change in bioactivity of a peptide, with the DAACP being the sole bioactive form. However, isomerization does not change the molecular weight of a peptide, making it difficult to detect using MS. Thus, bioactive peptides are likely hiding in neuropeptidomics study under the assumption that these peptides, like the majority of life, are formed solely of L-amino acids. Understanding the physiological purpose of DAACPs requires their further discovery. An approach to characterize unknown DAACPs, the DAACP discovery funnel, is presented in this work. It aims to solve this problem through a series of adapted MS-based analytical techniques capable of identifying potential DAACPs and assaying their amino acids for their chiral state. The discovery funnel is used to discover new DAACPs in the Aplysia californica nervous system and is applied, as pioneering work, to nervous system structures in rodents.","Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2019-05-01","The student, Itamar Livnat, accepted the attached license on 2017-04-02 at 23:57.","The student, Itamar Livnat, submitted this Dissertation for approval on 2017-04-03 at 00:08.","This Dissertation was approved for publication on 2017-04-03 at 11:36.","DSpace SAF Submission Ingestion Package generated from Vireo submission #10617 on 2017-08-10 at 15:05:02","Made available in DSpace on 2017-08-10T20:32:41Z (GMT). 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