Covalent attachment of ligands to nucleophilic proteins guided by non-covalent

摘要

A covalently reactive ligand analogue (CAL) of formula (1): wherein, L1 . . . Lx . . . Lm are components defining a ligand determinant, Lx is a component unit of the ligand determinant selected from the group consisting of an amino acid residue, sugar residue, a fatty acid residue and a nucleotide, L′ is a functional group of Lx, Y″ is atom, covalent bond or linker, Y′ is an optional charged or neutral group Y is a covalently reactive electrophilic group that reacts specifically with a receptor that binds to said ligand determinant, and n is an integer from 1 to 1000 m is an integer from 1 to 30.

主权项

1. A ligand analog that binds covalently to a nucleophilic receptor (NuR), wherein said ligand analog has the formula
L−Ewherein L is a ligand that binds noncovalently to a NuR, wherein L comprises a continuous or discontinuous epitope that binds noncovalently to said NuR, and E is an electrophilic group conjugated to a functional group of an amino acid side chain of L having the formula
Y−Y′−Y″−wherein
Y is an electrophilic group that reacts covalently with NuR, Y′ is a charged or neutral group, or is absent, and Y″ is a linker, covalent bond or atom.