Feasibility of a stereoselective synthesis of [11C](S, S)-S-adenosylmethionine ([11C](S,S)-SAM) catalyzed by an immobilized enzyme
This work aims to develop a stereoselective enzymatic alternative for the radiosynthesis of [11C](S,S)-S-ade-nosylmethionine ([11C](S,S)-SAM), a potential PET-CT radiotracer for monitoring particularly aggressive prostate tumors. Conventional synthesis of this compound has been carried out at Urugua...
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| Format: | article |
| Language: | English |
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2024
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| Online Access: | https://hdl.handle.net/20.500.12381/5578 https://doi.org/10.1016/j.procbio.2024.12.006 |
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| _version_ | 1868890179490545664 |
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| author | Diego, Umpiérrez Puchalvert |
| author2 | Florencia, Zoppolo Manuela Bentura Agustin, Castilla Eduardo, Savio Sonia, Rodríguez Giordano Gabriela, Irazoqui |
| author2_role | author author author author author author |
| author_browse | Agustin, Castilla Diego, Umpiérrez Puchalvert Eduardo, Savio Florencia, Zoppolo Gabriela, Irazoqui Manuela Bentura Sonia, Rodríguez Giordano |
| author_facet | Diego, Umpiérrez Puchalvert Florencia, Zoppolo Manuela Bentura Agustin, Castilla Eduardo, Savio Sonia, Rodríguez Giordano Gabriela, Irazoqui |
| author_role | author |
| collection | REDI |
| dc.creator.none.fl_str_mv | Diego, Umpiérrez Puchalvert Florencia, Zoppolo Manuela Bentura Agustin, Castilla Eduardo, Savio Sonia, Rodríguez Giordano Gabriela, Irazoqui |
| dc.date.none.fl_str_mv | 2024-12-07 2026-06-09T16:58:44Z 2026-06-09T16:58:44Z |
| dc.identifier.none.fl_str_mv | https://hdl.handle.net/20.500.12381/5578 FMV_1_2021_1_169507 https://doi.org/10.1016/j.procbio.2024.12.006 |
| dc.language.none.fl_str_mv | eng |
| dc.publisher.none.fl_str_mv | Elsevier |
| dc.relation.none.fl_str_mv | https://hdl.handle.net/20.500.12381/5517 https://hdl.handle.net/20.500.12381/5529 https://hdl.handle.net/20.500.12381/5562 |
| dc.rights.none.fl_str_mv | Acceso abierto info:eu-repo/semantics/openAccess Reconocimiento-NoComercial-SinObraDerivada 4.0 Internacional. (CC BY-NC-ND) |
| dc.source.none.fl_str_mv | Process Biochemistry reponame:REDI instname:Agencia Nacional de Investigación e Innovación instacron:Agencia Nacional de Investigación e Innovación |
| dc.subject.none.fl_str_mv | Enzymatic radiosynthesis SAM S-adenosylmethionine Methionine adenosyltransferase Immobilized enzyme Prostate cancer radiotracer Stereospecificity Ciencias Naturales y Exactas Ciencias Químicas |
| dc.title.none.fl_str_mv | Feasibility of a stereoselective synthesis of [11C](S, S)-S-adenosylmethionine ([11C](S,S)-SAM) catalyzed by an immobilized enzyme |
| dc.type.none.fl_str_mv | Artículo info:eu-repo/semantics/article Borrador info:eu-repo/semantics/draft |
| description | This work aims to develop a stereoselective enzymatic alternative for the radiosynthesis of [11C](S,S)-S-ade-nosylmethionine ([11C](S,S)-SAM), a potential PET-CT radiotracer for monitoring particularly aggressive prostate tumors. Conventional synthesis of this compound has been carried out at Uruguayan Center of Molecular Imaging, resulting in an almost racemic mixture 53:47 ratio of (R,S) to (S,S) isomer. Producing the radiotracer in an optically pure form is a requirement for administration to humans and additionally it would enhance diagnostic sensitivity when administered to the patient. The main challenges were designing a biocatalyst capable of withstanding the harsh conditions of the radiotracer synthesis module and achieving the reaction in a very short time due to the rapid decay of 11C. A mutant of E. coli methionine adenosyltransferase (I303V MAT) with enhanced SAM synthesis was cloned, expressed, and immobilized on agarose using an irreversible covalent isourea bond. This immobilized enzyme synthesized [11C](S,S)-SAM from [11C]L-methionine in an automated module, with the labeled methionine produced in situ from [11C]CH3I and L-homocysteine thiolactone. The product was obtained with an enantio and diasteromeric excess greater than 99 % and average conversion of 80 %. The reuse of the immobilized enzyme was studied, showing that after three cycles of reuse the radiosynthesis performance remained unchanged. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | anni_be3c04035233ffd0b267cb0316dce676 |
| identifier_str_mv | FMV_1_2021_1_169507 |
| instacron_str | Agencia Nacional de Investigación e Innovación |
| institution | Agencia Nacional de Investigación e Innovación |
| instname_str | Agencia Nacional de Investigación e Innovación |
| language | eng |
| network_acronym_str | anni |
| network_name_str | oai-lr-anni |
| oai_identifier_str | oai:redi.anii.org.uy:20.500.12381/5578 |
| publishDate | 2024 |
| publishDateSort | 2024 |
| publisher.none.fl_str_mv | Elsevier |
| reponame_str | REDI |
| repository.mail.fl_str_mv | |
| repository.name.fl_str_mv | |
| repository_id_str | |
| rights_invalid_str_mv | Acceso abierto Reconocimiento-NoComercial-SinObraDerivada 4.0 Internacional. (CC BY-NC-ND) |
| spelling | Feasibility of a stereoselective synthesis of [11C](S, S)-S-adenosylmethionine ([11C](S,S)-SAM) catalyzed by an immobilized enzymeDiego, Umpiérrez PuchalvertFlorencia, ZoppoloManuela BenturaAgustin, CastillaEduardo, SavioSonia, Rodríguez GiordanoGabriela, IrazoquiEnzymatic radiosynthesisSAMS-adenosylmethionineMethionine adenosyltransferaseImmobilized enzymeProstate cancer radiotracerStereospecificityCiencias Naturales y ExactasCiencias QuímicasThis work aims to develop a stereoselective enzymatic alternative for the radiosynthesis of [11C](S,S)-S-ade-nosylmethionine ([11C](S,S)-SAM), a potential PET-CT radiotracer for monitoring particularly aggressive prostate tumors. Conventional synthesis of this compound has been carried out at Uruguayan Center of Molecular Imaging, resulting in an almost racemic mixture 53:47 ratio of (R,S) to (S,S) isomer. Producing the radiotracer in an optically pure form is a requirement for administration to humans and additionally it would enhance diagnostic sensitivity when administered to the patient. The main challenges were designing a biocatalyst capable of withstanding the harsh conditions of the radiotracer synthesis module and achieving the reaction in a very short time due to the rapid decay of 11C. A mutant of E. coli methionine adenosyltransferase (I303V MAT) with enhanced SAM synthesis was cloned, expressed, and immobilized on agarose using an irreversible covalent isourea bond. This immobilized enzyme synthesized [11C](S,S)-SAM from [11C]L-methionine in an automated module, with the labeled methionine produced in situ from [11C]CH3I and L-homocysteine thiolactone. The product was obtained with an enantio and diasteromeric excess greater than 99 % and average conversion of 80 %. The reuse of the immobilized enzyme was studied, showing that after three cycles of reuse the radiosynthesis performance remained unchanged.Agencia Nacional de Investigación e InnovaciónElsevier2026-06-09T16:58:44Z2026-06-09T16:58:44Z2024-12-07Artículoinfo:eu-repo/semantics/articleBorradorinfo:eu-repo/semantics/drafthttps://hdl.handle.net/20.500.12381/5578FMV_1_2021_1_169507https://doi.org/10.1016/j.procbio.2024.12.006Process Biochemistryreponame:REDIinstname:Agencia Nacional de Investigación e Innovacióninstacron:Agencia Nacional de Investigación e Innovaciónenghttps://hdl.handle.net/20.500.12381/5517https://hdl.handle.net/20.500.12381/5529https://hdl.handle.net/20.500.12381/5562Acceso abiertoinfo:eu-repo/semantics/openAccessReconocimiento-NoComercial-SinObraDerivada 4.0 Internacional. (CC BY-NC-ND)oai:redi.anii.org.uy:20.500.12381/55782026-06-16T05:03:35Z |
| spellingShingle | Feasibility of a stereoselective synthesis of [11C](S, S)-S-adenosylmethionine ([11C](S,S)-SAM) catalyzed by an immobilized enzyme Diego, Umpiérrez Puchalvert Enzymatic radiosynthesis SAM S-adenosylmethionine Methionine adenosyltransferase Immobilized enzyme Prostate cancer radiotracer Stereospecificity Ciencias Naturales y Exactas Ciencias Químicas |
| status_str | draft |
| title | Feasibility of a stereoselective synthesis of [11C](S, S)-S-adenosylmethionine ([11C](S,S)-SAM) catalyzed by an immobilized enzyme |
| title_full | Feasibility of a stereoselective synthesis of [11C](S, S)-S-adenosylmethionine ([11C](S,S)-SAM) catalyzed by an immobilized enzyme |
| title_fullStr | Feasibility of a stereoselective synthesis of [11C](S, S)-S-adenosylmethionine ([11C](S,S)-SAM) catalyzed by an immobilized enzyme |
| title_full_unstemmed | Feasibility of a stereoselective synthesis of [11C](S, S)-S-adenosylmethionine ([11C](S,S)-SAM) catalyzed by an immobilized enzyme |
| title_short | Feasibility of a stereoselective synthesis of [11C](S, S)-S-adenosylmethionine ([11C](S,S)-SAM) catalyzed by an immobilized enzyme |
| title_sort | Feasibility of a stereoselective synthesis of [11C](S, S)-S-adenosylmethionine ([11C](S,S)-SAM) catalyzed by an immobilized enzyme |
| topic | Enzymatic radiosynthesis SAM S-adenosylmethionine Methionine adenosyltransferase Immobilized enzyme Prostate cancer radiotracer Stereospecificity Ciencias Naturales y Exactas Ciencias Químicas |
| url | https://hdl.handle.net/20.500.12381/5578 https://doi.org/10.1016/j.procbio.2024.12.006 |