Publication:
Synthesis and Biological Activity of Homohypotaurine Obtained by the Enzyme-Based Conversion of Homocysteine Sulfinic Acid Using Recombinant <i>Escherichia Coli</i> Glutamate Decarboxylase

dc.contributor.authorFontana M.
dc.contributor.authorGÜNAYDIN AKYILDIZ A.
dc.contributor.authorD'Alonzo C.
dc.contributor.authorGiovannercole F.
dc.contributor.authorZicchi A.
dc.contributor.authorFrancioso A.
dc.contributor.authorCapuozzo E.
dc.contributor.authorDe Biase D.
dc.date.accessioned2024-10-08T21:50:23Z
dc.date.available2024-10-08T21:50:23Z
dc.date.issued2024-09-01
dc.description.abstractL-Homocysteine, formed from S-adenosyl methionine following demethylation and adenosine release, accumulates when the methionine recycling pathway and other pathways become impaired, thus leading to hyperhomocysteinemia, a biomarker in cardiovascular diseases, neurological/psychiatric disorders, and cancer. The partial oxidation of the l-homocysteine thiol group and its decarboxylation on C-alpha lead to the formation of L-homocysteinesulfinic acid (L-HCSA) and homohypotaurine (HHT), respectively. Both compounds are not readily available from commercial suppliers, which hinders the investigation of their biological activities. Herein, the chemical synthesis of l-HCSA, from L-homocystine, was the starting point for establishing the bio-based synthesis of HHT using recombinant Escherichia coli glutamate decarboxylase (EcGadB), an enzyme already successfully employed for the bio-based synthesis of GABA and its phosphinic analog. Prior to HHT synthesis, k(cat) (33.92 +/- 1.07) and K-M (38.24 +/- 3.45 mM) kinetic constants were determined for L-HCSA on EcGadB. The results of our study show that the EcGadB-mediated synthesis of HHT can be achieved with good yields (i.e., 40% following enzymatic synthesis and column chromatography). Purified HHT was tested in vitro on primary human umbilical vein endothelial cells and rat cardiomyoblasts and compared to the fully oxidized analog, homotaurine (OT, also known as tramiprosate), in widespread pharmaceutical use. The results show that both cell lines display statistically significant recovery from the cytotoxic effects induced by H2O2 in the presence of HHT.
dc.identifier.citationFontana M., GÜNAYDIN AKYILDIZ A., D'Alonzo C., Giovannercole F., Zicchi A., Francioso A., Capuozzo E., De Biase D., "Synthesis and Biological Activity of Homohypotaurine Obtained by the Enzyme-Based Conversion of Homocysteine Sulfinic Acid Using Recombinant <i>Escherichia Coli</i> Glutamate Decarboxylase", MOLECULES, cilt.29, sa.17, 2024
dc.identifier.doi10.3390/molecules29173985
dc.identifier.issn1420-3049
dc.identifier.issue17
dc.identifier.pubmed39274833
dc.identifier.scopus85203641442
dc.identifier.urihttps://avesis.bezmialem.edu.tr/api/publication/d0becb32-8cca-476a-9b79-46457fd19971/file
dc.identifier.urihttps://hdl.handle.net/20.500.12645/39707
dc.identifier.volume29
dc.identifier.wosWOS:001311666000001
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectYaşam Bilimleri
dc.subjectMoleküler Biyoloji ve Genetik
dc.subjectSitogenetik
dc.subjectKimya
dc.subjectBiyokimya
dc.subjectAlkoloidler
dc.subjectTemel Bilimler
dc.subjectLife Sciences
dc.subjectMolecular Biology and Genetics
dc.subjectCytogenetic
dc.subjectChemistry
dc.subjectBiochemistry
dc.subjectAlcaloides
dc.subjectNatural Sciences
dc.subjectMoleküler Biyoloji Ve Genetik
dc.subjectTemel Bilimler (Sci)
dc.subjectKimya Multidisipliner
dc.subjectYaşam Bilimleri (Life)
dc.subjectBiyokimya Ve Moleküler Biyoloji
dc.subjectMolecular Biology & Genetics
dc.subjectNatural Sciences (Sci)
dc.subjectChemistry Multidisciplinary
dc.subjectLife Sciences (Life)
dc.subjectBiochemistry & Molecular Biology
dc.subjectİlaç Keşfi
dc.subjectKimya (çeşitli)
dc.subjectGenel Kimya
dc.subjectYapısal Biyoloji
dc.subjectMoleküler Biyoloji
dc.subjectKlinik Biyokimya
dc.subjectKanser Araştırmaları
dc.subjectYaşlanma
dc.subjectBiyokimya, Genetik ve Moleküler Biyoloji (çeşitli)
dc.subjectGenel Biyokimya, Genetik ve Moleküler Biyoloji
dc.subjectFizik Bilimleri
dc.subjectDrug Discovery
dc.subjectChemistry (miscellaneous)
dc.subjectGeneral Chemistry
dc.subjectStructural Biology
dc.subjectMolecular Biology
dc.subjectClinical Biochemistry
dc.subjectCancer Research
dc.subjectAging
dc.subjectBiochemistry, Genetics and Molecular Biology (miscellaneous)
dc.subjectGeneral Biochemistry, Genetics and Molecular Biology
dc.subjectPhysical Sciences
dc.titleSynthesis and Biological Activity of Homohypotaurine Obtained by the Enzyme-Based Conversion of Homocysteine Sulfinic Acid Using Recombinant <i>Escherichia Coli</i> Glutamate Decarboxylase
dc.typearticle
dspace.entity.typePublication
local.avesis.idd0becb32-8cca-476a-9b79-46457fd19971
local.indexed.atPubMed
local.indexed.atWOS
local.indexed.atScopus

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