摘要:
A method for site-selective acyl transfer in or amidation of folded polypeptides and proteins based on the use of a chemical structure element comprising an imidazole function, such as histidine, in position i flanked by at least one functional group to be amidated, such as lysine, in position i+3+4k, where k is an integer equal to or higher than -1, or in position i-4-4n, wherein n is an integer equal to or higher than 0, and at least one activating group, such as serine, in position i+4+4n or i-3-4n, respectively.
摘要:
An α-hydrazino acid derivative of general formula (I) is described, wherein R1, R2, R3 are hydrogen or a carbon radical, such that when R2 and R3 are different, C* is an asymmetric carbon of L, D or DL configuration, and R4 and R5 are a protecting group, characterised in that R4 is a benzyl ArCH2 radical of formula (a), wherein Ar is a phenyl radical or phenyl substituted by one or more X groups; X being hydrogen, halogen, a nitro or alkyl radical; and in that R5 is a Y-O-CO group, where Y is a carbon radical different from R4.
摘要:
The present invention describes a site specific conjugation method for glycoproteins wherein a stable dihydrazone bond is formed between the glycoproteins and the glycoproteins retain full activity. Also described is a novel glycoprotein-glycoprotein conjugate of the formula I wherein X and Y are glycoproteins modified such that the vicinal hydroxyl groups of the carbohydrate moieties in the glycoproteins have been oxidized to aldehydes which are then reacted with a hydrazide functional group to form a hydrazone bond which is represented in Formula I by "-C=NNH-".
摘要:
The invention provides for a chemical method for preparing a recombinant single copy polypeptide or a portion thereof with a modified terminal amino acid α-carbon reactive group selected from the group consisting of N-terminal α-amine, C-terminal α-carboxyl, and a combination thereof. The steps of the method involve forming the recombinant single copy polypeptide or a portion thereof so that the single copy polypeptide is protected with one or more biologically added protecting groups at the N-terminal α-amine, C-terminal α-carboxyl. The recombinant single copy polypeptide can then be reacted with up to three chemical protecting agents to selectively protect reactive side chain groups and thereby prevent side chain groups from being modified. The recombinant single copy polypeptide can be cleaved with at least one cleavage reagent specific for the biological protecting group to form an unprotected terminal amino acid α-carbon reactive group. The unprotected terminal amino acid α-carbon reactive group is modified with at least one chemical modifying agent. The side chain protected terminally modified single copy polypeptide is then deprotected at the side chain groups to form a terminally modified recombinant single copy polypeptide. The number and sequence of steps in the method can be varied to achieve selective modification at the N- and/or C-terminal amino acid of a recombinantly produced polypeptide.
摘要:
Protein derivatives of formula (1) A-CO-N(R¹)CH₂-Z-R² (1) wherein A-CO is the residue of a protein or peptide A-CO₂H (especially where -CO₂H is the C-terminal carboxyl group of the protein or peptide); R¹ is a hydrogen atom or an alkyl, aryl or aralkyl group; Z¹, which may be present or absent is a spacer group; R² is a group -C(OH)(R³)CH₂NHR⁴ or -C(R³)O (where R³ and R⁴ which may be the same or different, is each a hydrogen atom or an alkyl, aryl or aralkyl group); with the proviso that when A-CO is a residue of insulin, R¹ is other than a hydrogen atom; and the salts thereof. The compounds may be prepared by a condensation reaction,, especially in the presence of an enzyme capable of catalysing the formation of a peptide bond. The compounds may be used to form protein conjugates in which a group of interest such as another protein or peptide or an effector or reporter group is coupled to the protein through a -N(R¹)CH₂-Z¹-C(OH)(R³)CH₂N= or -N(R¹)CH₂Z¹-CH= group.
摘要:
Protein derivatives of formula (1) A-CO-N(R 1 )N(R 2 )-Z 1 - wherein A-CO is the residue of a protein or peptide A-CO 2 H (especially where -C0 2 H is the C-terminal carboxyl group of the protein or peptide); R 1 , R 2 , R 3 and R 4 , which may be the same or different, and which may be present or absent, is each a spacer group, X is an oxygen or sulphur atom; and the salts thereof. The compounds may be prepared by a condensation reaction, especially in the presence of an enzyme capable of catalysing the formation of a peptide bond. The compounds may be used to form protein conjugates in which a group of interest such as another protein or peptide or an effector or reporter group is coupled to the protein through a -N-(R 1 )N(R 2 )-Z 1 -C(=X)-Z 2 -N(R 3 )N= group.
摘要:
The invention provides a method for conjugating a peptide displayed on a genetic display system to a molecular scaffold performed on an ion exchange resin.