{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T09:48:26Z","timestamp":1790761706121,"version":"4.1.0"},"reference-count":30,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2006,5,9]],"date-time":"2006-05-09T00:00:00Z","timestamp":1147132800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Chemistry A European J"],"published-print":{"date-parts":[[2006,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Homocysteine thiolactone (tHcy) is deemed a risk factor for cardiovascular diseases and strokes, presumably because it acylates the side chain of protein lysine residues (\u201cN\u2010homocysteinylation\u201d), thereby causing protein damage and autoimmune responses. We analysed the kinetics of hydrolysis and aminolysis of tHcy and two related thiolactones (\u03b3\u2010thiobutyrolactone and <jats:italic>N<\/jats:italic>\u2010trimethyl\u2010tHcy), and we have thereby described the first detailed mechanism of thiolactone aminolysis. As opposed to the previously studied (thio and oxo)esters and (oxo)lactones, aminolysis of thiolactones was found to be first order with respect to amine concentration. Anchimeric assistance by the \u03b1\u2010amino group of tHcy (through general acid\/base catalysis) could not be detected, and the Br\u00f8nsted plot (nucleophilicity versus p<jats:italic>K<\/jats:italic><jats:sub>a<\/jats:sub>) for aminolysis yielded a slope (\u03b2<jats:sup>nuc<\/jats:sup>) value of 0.66. These data support a mechanism of aminolysis where the rate\u2010determining step is the formation of a zwitterionic tetrahedral intermediate. The \u03b2<jats:sup>nuc<\/jats:sup> value and steric factors dictate a regime whereby, at physiological pH values (pH 7.4), maximal reactivity of tHcy is exhibited with primary amine groups with a p<jats:italic>K<\/jats:italic><jats:sub>a<\/jats:sub> value of 7.7; this allows the reactivity of various protein amino groups towards N\u2010homocysteinylation to be predicted.<\/jats:p>","DOI":"10.1002\/chem.200501145","type":"journal-article","created":{"date-parts":[[2006,2,2]],"date-time":"2006-02-02T04:17:42Z","timestamp":1138853862000},"page":"4144-4152","source":"Crossref","is-referenced-by-count":33,"title":["Mechanism of Hydrolysis and Aminolysis of Homocysteine Thiolactone"],"prefix":"10.1002","volume":"12","author":[{"given":"Jonathan","family":"Garel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan S.","family":"Tawfik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,5,9]]},"reference":[{"key":"e_1_2_6_1_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.63.s84.33.x"},{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-003-3204-7"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.13.15.2277"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.6.3957"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.87.1.45"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M313268200"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0020-7055(74)90033-3"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja01589a025"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1021\/ol006691l"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja01488a043"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo01351a086"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja01488a044"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja00339a013"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja00829a034"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja00436a022"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1039\/tf9504600723"},{"key":"e_1_2_6_17_2","volume-title":"Dissociation constants of organic bases in aqueous solutions","author":"Perrin D. D.","year":"1965"},{"key":"e_1_2_6_18_2","volume-title":"CRC handbook of chemistry and physics","year":"2002"},{"key":"e_1_2_6_19_2","volume-title":"Critical stability constants,","author":"Smith R. M.","year":"1990"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo0103017"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/recl.19760950102"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-3160(08)60129-X"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1039\/c39870001775"},{"key":"e_1_2_6_24_2","first-page":"239","volume":"4","author":"Kaiser E. T.","year":"1976","journal-title":"Prog. Bioorg. Chem."},{"key":"e_1_2_6_25_2","first-page":"16","volume-title":"All about albumin","author":"Peters T.","year":"1996"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00783a023"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja00834a029"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo015723v"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1002\/1521-3765(20020816)8:16<3687::AID-CHEM3687>3.0.CO;2-8"},{"key":"e_1_2_6_30_2","unstructured":"Equation (6) is rigorously correct only if \u03b2nuc(tHcy\u00b0)=\u03b2nuc(tHcyH+). Since \u03b2nuc(tHcyH+) could not be measured with accuracy its contribution was not taken into account. This hardly affects the results exposed thereafter because \u03b2nuc(tHcy\u00b0) and \u03b2nuc(tHcyH+) differ only slightly."}],"container-title":["Chemistry \u2013 A European Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fchem.200501145","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/chem.200501145","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T20:27:47Z","timestamp":1760300867000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/chem.200501145"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,5,9]]},"references-count":30,"journal-issue":{"issue":"15","published-print":{"date-parts":[[2006,5,15]]}},"alternative-id":["10.1002\/chem.200501145"],"URL":"https:\/\/doi.org\/10.1002\/chem.200501145","archive":["Portico"],"relation":{},"ISSN":["0947-6539","1521-3765"],"issn-type":[{"value":"0947-6539","type":"print"},{"value":"1521-3765","type":"electronic"}],"subject":[],"published":{"date-parts":[[2006,5,9]]}}}