Traceless reductively cleavable linker molecules for peptide purification
AssigneeGyros Protein Technologies AB
InventorsRobert Zitterbart, Oliver Reimann
Life of this patent
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Abstract
The present invention relates to linker molecules of formula (1), X-Tb-Va—U—Y—Z (1) and a method for purifying peptides using said linker molecules. The linker molecule can be coupled to a purification resin via the moiety X and to a peptide via the moiety Y under the release of the leaving group Z. T is an optional spacer moiety and V is an optional electron withdrawing moiety. U is an aryl or 5- or 6-membered heteroaryl moiety bound to at least one electron withdrawing moiety V, W or E. The linker is stable under acidic conditions and releases the peptide upon addition of a reducing agent.
Claims14
A compound of formula 1, X-T-V—U—Y—Z (1), wherein
- X is a moiety of formula 2,
- wherein
- each R1 and R2 is independently from each other selected from a group consisting of H or B, wherein at least R1 or R2 is B,
- B is an acid labile amine protecting group selected from a group consisting of Boc (—C(═O)OtBu), Eei (═CMeOEt, 1-ethoxyethylidene) trityl (—C(Ph)3), —C(═O)CPh3, Mmt (—C(Ph)2C6H4OMe), DMT (—C(Ph)(C6H4OMe)2), Cbz (—C(═O)OCH2Ph), benzylideneamine (═CPh), phtalimides (═(CO)2C6H4), p-toluenesulfonamides (—SO2C6H4Me), benzylamine (—CH2Ph), acetamides (—COMe), trifluoroacetamide (—COCF3), Dde (1-(4,4-dimethyl-2,6-dioxocyclohex-1-ylidene)-3-ethyl) and 1-(4,4-dimethyl-2,6-dioxocyclohex-1-ylidene)-3-methylbutyl (ivDde), wherein particularly B is Boc or Eei,
- T is a spacer selected from a group consisting of
- C1-3-alkyl, —R5—C(═O)—, and —R5—C(═O)—NR9—R6—, wherein
- R5, and R6 are independently from each other selected from a group consisting of C1-C3 alkyl, and wherein
- R9 is H, V is an electron-withdrawing moiety selected from a group consisting of —NR11—C(═O)—, —C(═O)—NR11—, and -piperazinyl-(CH2)p—, wherein,
- R11 is selected from a group consisting of H and C1-2-alkyl, and
- p is 0 or 1,
- U is a phenyl, that is bound to at least one of the moieties Wq and En wherein
- W is selected from a group consisting of —N3, —NO2, —S—S—R8, wherein
- R8 is pyridyl or —C1-C6-alkyl,
- E is an electron withdrawing group under acidic conditions,
- n being is an integer between 0 and 2, and q is 1, and wherein
- W is in ortho or para position in relation to Y,
- Y is —(CH2)—C(═O)— or —(CH2)—O—C(═O)—, and
- Z is an electron-withdrawing leaving group selected from a group consisting of —OH and
Dependencies are inferred from the claim text.