{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1360004233254218752.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1021/tx400469x"}},{"identifier":{"@type":"URI","@value":"https://pubs.acs.org/doi/pdf/10.1021/tx400469x"}},{"identifier":{"@type":"PMID","@value":"24568234"}}],"resourceType":"学術雑誌論文(journal article)","dc:title":[{"@value":"N-Terminal α-Ketoamide Peptides: Formation and Transamination"}],"description":[{"notation":[{"@value":"We have previously reported that N-terminal α-ketoamide peptides can be formed through 4-oxo-2(E)-nonenal (ONE)-derived oxidative decarboxylation of aspartic acid (Asp), which converts angiotensin (Ang) II (DRVYIHPF) to pyruvamide-Ang II (Ang P, CH3COCONH-RVYIHPF). The pyruvamide group significantly inhibits Ang P binding to the Ang II type 1 receptor, which mediates the major biological effects of Ang II. In the present study, we found that ONE can also introduce an α-ketoamide moiety at the N-terminus of peptides containing N-terminal residues other than Asp. Subsequent investigation of alternative biosynthetic pathways for N-terminal α-ketoamide peptides revealed that hydroxyl radical-mediated formation is a much more efficient route. The proposed mechanism involves initial abstraction of the N-terminal α-hydrogen and hydrolysis of the ketimine intermediate. The resulting N-terminal α-ketoamide is then converted to the D- and L-amino acids by nonenzymatic transamination in the presence of pyridoxamine (PM). The formation of the epimeric N-terminus depended on the incubation time and the concentration of PM, and increased further upon the addition of Cu(II) ions. A conversion of approximately 60% after three days of incubation was observed for Ang P. We propose that the reaction intermediate contains a prochiral α-carbon and is stabilized by the chelate effect of Cu(II) ions. The ONE- and hydroxyl radical-derived formation of N-terminal α-ketoamide and its transamination in the presence of PM were also observed in amyloid β 1-11 (DAEFRHDSGYE), where the N-terminal Asp was converted to epimeric alanine. This suggests that these N-terminal modifications could occur in vivo and modulate the biological functions of peptides and proteins."}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1380004233254218753","@type":"Researcher","foaf:name":[{"@value":"Seon Hwa Lee"}],"jpcoar:affiliationName":[{"@value":"Department of Bio-analytical\rChemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Aobayama,\rAoba-ku, Sendai 980-8578, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1380004233254218754","@type":"Researcher","foaf:name":[{"@value":"Hyunsook Kyung"}],"jpcoar:affiliationName":[{"@value":"Department of Bio-analytical\rChemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Aobayama,\rAoba-ku, Sendai 980-8578, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1380004233254218756","@type":"Researcher","foaf:name":[{"@value":"Ryo Yokota"}],"jpcoar:affiliationName":[{"@value":"Department of Bio-analytical\rChemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Aobayama,\rAoba-ku, Sendai 980-8578, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1380004233254218755","@type":"Researcher","foaf:name":[{"@value":"Takaaki Goto"}],"jpcoar:affiliationName":[{"@value":"Department of Bio-analytical\rChemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Aobayama,\rAoba-ku, Sendai 980-8578, Japan"}]},{"@id":"https://cir.nii.ac.jp/crid/1420564276170294784","@type":"Researcher","personIdentifier":[{"@type":"KAKEN_RESEARCHERS","@value":"10203712"},{"@type":"NRID","@value":"1000010203712"},{"@type":"NRID","@value":"9000253160829"},{"@type":"NRID","@value":"9000001615058"},{"@type":"NRID","@value":"9000005188391"},{"@type":"NRID","@value":"9000254234933"},{"@type":"NRID","@value":"9000005267767"},{"@type":"NRID","@value":"9000254694335"},{"@type":"NRID","@value":"9000415200307"},{"@type":"NRID","@value":"9000283300457"},{"@type":"NRID","@value":"9000005258088"},{"@type":"NRID","@value":"9000000265268"},{"@type":"NRID","@value":"9000001042907"},{"@type":"NRID","@value":"9000403426179"},{"@type":"NRID","@value":"9000392643267"},{"@type":"NRID","@value":"9000252809356"},{"@type":"NRID","@value":"9000258576254"},{"@type":"RESEARCHMAP","@value":"https://researchmap.jp/read0138585"}],"foaf:name":[{"@value":"Tomoyuki Oe"}],"jpcoar:affiliationName":[{"@value":"Department of Bio-analytical\rChemistry, Graduate School of Pharmaceutical Sciences, Tohoku University, Aobayama,\rAoba-ku, Sendai 980-8578, Japan"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"0893228X"},{"@type":"EISSN","@value":"15205010"}],"prism:publicationName":[{"@value":"Chemical Research in Toxicology"}],"dc:publisher":[{"@value":"American Chemical Society (ACS)"}],"prism:publicationDate":"2014-02-25","prism:volume":"27","prism:number":"4","prism:startingPage":"637","prism:endingPage":"648"},"reviewed":"false","url":[{"@id":"https://pubs.acs.org/doi/pdf/10.1021/tx400469x"}],"createdAt":"2014-02-14","modifiedAt":"2023-04-18","foaf:topic":[{"@id":"https://cir.nii.ac.jp/all?q=Spectrometry,%20Mass,%20Electrospray%20Ionization","dc:title":"Spectrometry, Mass, Electrospray Ionization"},{"@id":"https://cir.nii.ac.jp/all?q=Tandem%20Mass%20Spectrometry","dc:title":"Tandem Mass Spectrometry"},{"@id":"https://cir.nii.ac.jp/all?q=Amino%20Acid%20Sequence","dc:title":"Amino Acid 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