Carboxymethyl-substituted bifunctional chelators: preparation of aryl isothiocyanate derivatives of 3-(carboxymethyl)-3-azapentanedioic acid, 3,12-bis(carboxymethyl)-6,9-dioxa-3,12-diazatetradecanedioic++ + acid, and 1,4,7,10-tetraazacyclododecane-N,N',N",N'''-tetraacetic acid for use as protein labels.
3-(Carboxymethyl)-3-azapentanedioic acid (NTA), 3,12-bis(carboxymethyl)-6,9-dioxa-3,12-diazatetradecanedioic acid (EGTA), and 1,4,7,10-tetraazacyclododecane-N,N',N",N'''-tetraacetic acid (DOTA) structures having a 4-nitrophenyl substituent attached via an alkyl spacer to the methylene carbon atom of one carboxymethyl arm of the chelator were obtained by alkylation of 4-nitrophenylalanine with bromoacetic acid (NTA), by reductive alkylation of 1,8-diamino-3,6-dioxaoctane with (4-nitrophenyl)-pyruvic acid followed by alkylation with bromoacetic acid (EGTA), and by alkylation of the trimethyl ester of 1,4,7,10-tetraazacyclododecane-N,N',N"-triacetic acid with the methyl ester of alpha-bromo-4-(4-nitrophenyl)pentanoic acid and subsequent saponification (DOTA). The nitrophenyl-substituted chelators were converted to the corresponding amines by hydrogenation then reacted with thiophosgene to give the protein-reactive aryl isothiocyanate derivatives.
Kline
S J
SJ
Abbott Laboratories, Department 90M, Abbott Park, Illinois 60064.
Betebenner
D A
DA
Johnson
D K
DK
D001372:Aza Compounds / Q000138:chemical synthesis*; D002264:Carboxylic Acids / Q000138:chemical synthesis*; D002614:Chelating Agents / Q000138:chemical synthesis*; D003432:Cross-Linking Reagents / Q000138:chemical synthesis*; D004492:Edetic Acid / Q000138:chemical synthesis*; D009571:Nitrilotriacetic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D013861:Thiocyanates / Q000138:chemical synthesis*
D001372:Aza Compounds; D002264:Carboxylic Acids; D002614:Chelating Agents; D003432:Cross-Linking Reagents; D013861:Thiocyanates; D004492:Edetic Acid; D009571:Nitrilotriacetic Acid