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Triazolecarbaldehyde Reagents for One‐Step N‐Terminal Protein Modification
Author(s) -
Onoda Akira,
Inoue Nozomu,
Sumiyoshi Eigo,
Hayashi Takashi
Publication year - 2020
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201900692
Subject(s) - chemistry , moiety , combinatorial chemistry , derivative (finance) , amine gas treating , protecting group , functional group , surface modification , stereochemistry , reagent , molecule , organic chemistry , alkyl , financial economics , economics , polymer
Abstract Site‐specific modification of peptides and proteins is a key aspect of protein engineering. We developed a method for modification of the N terminus of proteins using 1 H ‐1,2,3‐triazole‐4‐carbaldehyde (TA4C) derivatives, which can be prepared in one step. The N‐terminal specific labeling of bioactive peptides and proteins with the TA4C derivatives proceeds under mild reaction conditions in excellent conversion (angiotensin I: 92 %, ribonuclease A: 90 %). This method enables site‐specific conjugation of various functional molecules such as fluorophores, biotin, and polyethylene glycol attached to the triazole ring to the N terminus. Furthermore, a functional molecule modified with a primary amine moiety can be directly converted into a TA4C derivative through a Dimroth rearrangement reaction with 1‐(4‐nitrophenyl)‐1 H ‐1,2,3‐triazole‐4‐carbaldehyde. This method can be used to obtain N‐terminal‐modified proteins via only two steps: 1) convenient preparation of a TA4C derivative with a functional group and 2) modification of the N terminus of the protein with the TA4C derivative.