Method using activated linker with specified functionality to modify components for coupling with thio-esters through chemical ligation, employs specified linker structure

摘要

Method using an activated linker with specified functionality to modify components for coupling with thio-esters through chemical ligation, is new. Method using an activated linker with specified functionality to modify components for coupling with thio-esters through chemical ligation, is new. The general linker structure is expressed as (1-amino-2-mercapto-functionality)-(spacer)-(reactive group). The linker formula includes 1-amino-2-mercapto functionality formed by the groups R1S and R2NH. R1S : is a mercapto group, e.g. S-t-butyl, S-t-butylthio, S-acetamidomethyl, S-benzyl, S-p-methylbenzyl, S-p-Methoxybenzyl, S-trityl, S-p-metoxytrityl, S-phenyl, S-diphenyl-methyl, S-carboxymethyl, S-alkyl and S-acetyl or another protected, partially-protected or unprotected mercapto group; R2NH : is an amino group, e.g. a NHFmoc-protective group (fluorenyl-methoxycarbonyl), NHBoc (t-butyloxycarbonyl), NHAc (acetyl), NHiBut (isobutyryl), NHTrt (trityl) and NHZ (benzyloxycarbonyl) or another protected, partially-protected or unprotected amino group; Spacer : is an aliphatic and aromatic chain, e.g. an oligo- and polyethylene glycol, of which the sulfur and nitrogen analogs are oligo- and polyamide, oligo and polyester or other long chain molecule groups; Reactive group functionality : is selected from: carbonic acids, activated carbonic acid derivatives, acid halogenides, active esters, alcohols, thiols, isocyanates, aldehydes, ketones, amines, imides, pyridyldisulfides, phosphoramidite and hydrazine. Products of conversion of the compound and the chemically-complementary first component are caused to react with a second component containing a thio-ester group. The conversion has the nature of a native chemical ligation (NCL).