{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/101796"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/101796","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Analysis of enzymatic L/D-peptide isomerization in animals","abstract":"The study of cell-to-cell signaling peptides contributes to the fundamental understanding of physiological processes and improves the effectiveness of pharmaceutical drugs. While protein synthesis in animals is stereospecific for all L-form amino acids, a unique and bioactive group of D-amino acid-containing peptides (DAACPs) have been found to exist in a broad array of animals. DAACPs result from a post-translational modification (PTM) in which an L-amino acid residue is enzymatically converted into a D-amino acid residue in the peptide chain. Isomerization leads to important changes in the three-dimensional structure and bioactivity of the DAACP and increases its resistance to degradation by peptidases. However, current research into peptide isomerization is limited because this PTM is not easily detected in mass spectrometry-based peptidomics experiments due to the lack of an associated mass shift. To address this challenge, we have developed a method for the non-targeted detection of DAACPs in biological samples and used it to explore the prevalence of DAACPs in the neurobiological model organism Aplysia californica. Two novel DAACPs were discovered using this method. Based on these results, it was hypothesized that an L/D-peptide isomerase exists in Aplysia which is responsible for the biosynthesis of DAACPs. An assay for isomerase activity was developed and used to partially purify and characterize an L/D-isomerase in the Aplysia central nervous system. Furthermore, isomerase activity was detected in multiple tissues in the rat, and a mammalian neuropeptide was found to be isomerized by this activity. These findings advance our understanding of the extent and function of enzymatic L/D-peptide isomerization as a PTM in bioactive peptides.","abstract_html":"The study of cell-to-cell signaling peptides contributes to the fundamental understanding of physiological processes and improves the effectiveness of pharmaceutical drugs. While protein synthesis in animals is stereospecific for all L-form amino acids, a unique and bioactive group of D-amino acid-containing peptides (DAACPs) have been found to exist in a broad array of animals. DAACPs result from a post-translational modification (PTM) in which an L-amino acid residue is enzymatically converted into a D-amino acid residue in the peptide chain. Isomerization leads to important changes in the three-dimensional structure and bioactivity of the DAACP and increases its resistance to degradation by peptidases. However, current research into peptide isomerization is limited because this PTM is not easily detected in mass spectrometry-based peptidomics experiments due to the lack of an associated mass shift. To address this challenge, we have developed a method for the non-targeted detection of DAACPs in biological samples and used it to explore the prevalence of DAACPs in the neurobiological model organism Aplysia californica. Two novel DAACPs were discovered using this method. Based on these results, it was hypothesized that an L/D-peptide isomerase exists in Aplysia which is responsible for the biosynthesis of DAACPs. An assay for isomerase activity was developed and used to partially purify and characterize an L/D-isomerase in the Aplysia central nervous system. Furthermore, isomerase activity was detected in multiple tissues in the rat, and a mammalian neuropeptide was found to be isomerized by this activity. These findings advance our understanding of the extent and function of enzymatic L/D-peptide isomerization as a PTM in bioactive peptides.","abstract_has_math":false,"creators":["Tai, Hua-Chia"],"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.","Yau, Peter M.","Raetzman, Lori T.","Christian, Catherine A."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2018,"date_issued":"2018-09-27T16:47:26Z","date_published":"2018-09-27T16:47:26Z","updated_at":"2026-07-22T22:24:40Z","subjects":["Neuropeptide","Chirality","Peptide isomerization","D-amino acid","Isomerase","Mass spectrometry (MS)","Liquid chromatography-mass spectrometry (LC-MS)"],"languages":["en"],"rights":["Copyright 2018 Hua-Chia Tai"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/2142/101796","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Sweedler, Jonathan V.","Yau, Peter M.","Raetzman, Lori T.","Christian, Catherine A."]},{"key":"dc:creator","label":"Author","values":["Tai, Hua-Chia"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2018-09-27T16:47:26Z","2020-09-28T09:15:16Z","2018-07-10","2018-08"]},{"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":["Neuropeptide","Chirality","Peptide isomerization","D-amino acid","Isomerase","Mass spectrometry (MS)","Liquid chromatography-mass spectrometry (LC-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 2018 Hua-Chia Tai"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/2142/101796"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["The study of cell-to-cell signaling peptides contributes to the fundamental understanding of physiological processes and improves the effectiveness of pharmaceutical drugs. While protein synthesis in animals is stereospecific for all L-form amino acids, a unique and bioactive group of D-amino acid-containing peptides (DAACPs) have been found to exist in a broad array of animals. DAACPs result from a post-translational modification (PTM) in which an L-amino acid residue is enzymatically converted into a D-amino acid residue in the peptide chain. Isomerization leads to important changes in the three-dimensional structure and bioactivity of the DAACP and increases its resistance to degradation by peptidases. However, current research into peptide isomerization is limited because this PTM is not easily detected in mass spectrometry-based peptidomics experiments due to the lack of an associated mass shift. To address this challenge, we have developed a method for the non-targeted detection of DAACPs in biological samples and used it to explore the prevalence of DAACPs in the neurobiological model organism Aplysia californica. Two novel DAACPs were discovered using this method. Based on these results, it was hypothesized that an L/D-peptide isomerase exists in Aplysia which is responsible for the biosynthesis of DAACPs. An assay for isomerase activity was developed and used to partially purify and characterize an L/D-isomerase in the Aplysia central nervous system. Furthermore, isomerase activity was detected in multiple tissues in the rat, and a mammalian neuropeptide was found to be isomerized by this activity. These findings advance our understanding of the extent and function of enzymatic L/D-peptide isomerization as a PTM in bioactive peptides.","Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2020-08-01","The student, Hua-Chia Tai, accepted the attached license on 2018-07-06 at 17:10.","The student, Hua-Chia Tai, submitted this Dissertation for approval on 2018-07-06 at 17:12.","This Dissertation was approved for publication on 2018-07-10 at 09:41.","DSpace SAF Submission Ingestion Package generated from Vireo submission #12763 on 2018-09-27 at 11:36:22","Made available in DSpace on 2018-09-27T16:47:26Z (GMT). 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While protein synthesis in animals is stereospecific for all L-form amino acids, a unique and bioactive group of D-amino acid-containing peptides (DAACPs) have been found to exist in a broad array of animals. DAACPs result from a post-translational modification (PTM) in which an L-amino acid residue is enzymatically converted into a D-amino acid residue in the peptide chain. Isomerization leads to important changes in the three-dimensional structure and bioactivity of the DAACP and increases its resistance to degradation by peptidases. However, current research into peptide isomerization is limited because this PTM is not easily detected in mass spectrometry-based peptidomics experiments due to the lack of an associated mass shift. To address this challenge, we have developed a method for the non-targeted detection of DAACPs in biological samples and used it to explore the prevalence of DAACPs in the neurobiological model organism Aplysia californica. Two novel DAACPs were discovered using this method. Based on these results, it was hypothesized that an L/D-peptide isomerase exists in Aplysia which is responsible for the biosynthesis of DAACPs. An assay for isomerase activity was developed and used to partially purify and characterize an L/D-isomerase in the Aplysia central nervous system. Furthermore, isomerase activity was detected in multiple tissues in the rat, and a mammalian neuropeptide was found to be isomerized by this activity. These findings advance our understanding of the extent and function of enzymatic L/D-peptide isomerization as a PTM in bioactive peptides.","Submission published under a 24 month embargo labeled 'Closed Access', the embargo will last until 2020-08-01","The student, Hua-Chia Tai, accepted the attached license on 2018-07-06 at 17:10.","The student, Hua-Chia Tai, submitted this Dissertation for approval on 2018-07-06 at 17:12.","This Dissertation was approved for publication on 2018-07-10 at 09:41.","DSpace SAF Submission Ingestion Package generated from Vireo submission #12763 on 2018-09-27 at 11:36:22","Made available in DSpace on 2018-09-27T16:47:26Z (GMT). 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