Traceless reductively cleavable linker molecules for peptide purification

A compound of formula 1, X-Tb-Va—U—Y—Z (1), wherein

• X is a moiety of formula 2
• wherein
• each R1 and R2 is independently from each other H or B, wherein at least R1 or R2 is B,
• B is an acid labile amine protecting group,
• T is a linear or branched spacer comprising 1 to 5 of the moieties selected from:
• —C1-12-alkyl-, (—C2H4O—)1-12, —C(═O)—, —C(═O)—JR9—, -JR9—C(═O)—, -JR9—, phenyl, 5- or 6-membered heteroaryl,
• J is CH or N,
• and wherein
• R9 is selected from the group consisting of H, C1-4-alkyl, —C1-6-alkyl-NH2, —C1-6-alkyl-NHB, —C1-6-alkyl-NB2, —R15, —C1-6-alkyl-R15, and —C1-6-alkyl-NH—R15, wherein
• B is an independently selected acid labile amine protecting group,
• R15 is a blocking agent that is able to react with an aldehyde moietyselected from the group consisting of cysteinyl, threoninyl, 2-mercaptoethanol, cysteamine, ethandithiole, hydroxylamine, O-methylhydroxylamine, N-methylhydroxylamine, dithiothreitol, and hydrazine, wherein:
• amine and/or thiol moieties of the blocking agent may be protected by an acid labile amine protecting group B, and/or an acid labile thiol protecting group,
• b is 0 or 1,
• V is an electron-withdrawing moiety selected from the group consisting of —NR11—C(═O)—, —C(═O)—NR11—, —S(═O)—, —NR12—(CH2)p—, -piperazinyl-(CH2)p—, -pyridinyl-, and pyrimidinyl, wherein
• R11 is selected from the group consisting of H and C1-4-alkyl,
• R12 is selected from the group consisting of H and C1-4-alkyl,
• p is 0, 1 or 2,
• a is 1, wherein the sum of a and b is 1 or 2,
• U is a phenyl or a five- or six-membered heteroaryl moiety, that is bound to at least one of the moieties V, Wq and En and that is unsubstituted or substituted by C1-6-alkyl, wherein
• V is defined as described above,
• W is selected from the group consisting of —N3, —NO2, —S(═O)—R8, —S—S—R8, —O—CH2—N3, —O—C(═O)—O—CH2—N3, —N═N-phenyl, —N═N—R8,
• wherein
• R8 is pyridyl, pyrimidinyl, pyrazinyl, pyridazyl, —C1-C6-alkyl or —(CH2)p—NMe2, p is 1, 2, 3 or 4,
• E is an electron withdrawing group under acidic conditions,
• n is an integer between 0 and 4, and q is an integer between 1 and 4, wherein the sum of n and q is equal or lower than 4, and wherein
• when U is a phenyl moiety and Y is —(CH2)m—O—C(═O)—, the sum of Hammett constants of V, W, E under acidic conditions is larger than 0.45, and wherein
• W is in ortho or para position in relation to Y,
• Y is —(CH2)m—C(═O)— or —(CH2)m—O—C(═O)—, m is 1, 2 or 3, and
• Z is an electron-withdrawing leaving group.