Highly Selective Lysine Acylation in Proteins Using a Lys-His Tag Sequence
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Highly Selective Lysine Acylation in Proteins Using a Lys-His Tag Sequence. / Kofoed, Christian; Wu, Shunliang; Sørensen, Kasper K.; Treiberg, Tuule; Arnsdorf, Johnny; Bjørn, Sara P.; Jensen, Tanja L.; Voldborg, Bjørn G.; Thygesen, Mikkel B.; Jensen, Knud J.; Schoffelen, Sanne.
I: Chemistry: A European Journal, Bind 28, Nr. 15, e202200147, 2022.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Highly Selective Lysine Acylation in Proteins Using a Lys-His Tag Sequence
AU - Kofoed, Christian
AU - Wu, Shunliang
AU - Sørensen, Kasper K.
AU - Treiberg, Tuule
AU - Arnsdorf, Johnny
AU - Bjørn, Sara P.
AU - Jensen, Tanja L.
AU - Voldborg, Bjørn G.
AU - Thygesen, Mikkel B.
AU - Jensen, Knud J.
AU - Schoffelen, Sanne
N1 - Publisher Copyright: © 2022 Wiley-VCH GmbH
PY - 2022
Y1 - 2022
N2 - Chemical modification of proteins has numerous applications, but it has been challenging to achieve the required high degree of selectivity on lysine amino groups. Recently, we described the highly selective acylation of proteins with an N-terminal Gly-His6 segment. This tag promoted acylation of the N-terminal Nα-amine resulting in stable conjugates. Herein, we report the peptide sequences Hisn-Lys-Hism, which we term Lys-His tags. In combination with simple acylating agents, they facilitate the acylation of the designated Lys Nϵ-amine under mild conditions and with high selectivity over native Lys residues. We show that the Lys-His tags, which are 7 to 10 amino acids in length and still act as conventional His tags, can be inserted in proteins at the C-terminus or in loops, thus providing high flexibility regarding the site of modification. Finally, the selective and efficient acylation of the therapeutic antibody Rituximab, pure or mixed with other proteins, demonstrates the scope of the Lys-His tag acylation method.
AB - Chemical modification of proteins has numerous applications, but it has been challenging to achieve the required high degree of selectivity on lysine amino groups. Recently, we described the highly selective acylation of proteins with an N-terminal Gly-His6 segment. This tag promoted acylation of the N-terminal Nα-amine resulting in stable conjugates. Herein, we report the peptide sequences Hisn-Lys-Hism, which we term Lys-His tags. In combination with simple acylating agents, they facilitate the acylation of the designated Lys Nϵ-amine under mild conditions and with high selectivity over native Lys residues. We show that the Lys-His tags, which are 7 to 10 amino acids in length and still act as conventional His tags, can be inserted in proteins at the C-terminus or in loops, thus providing high flexibility regarding the site of modification. Finally, the selective and efficient acylation of the therapeutic antibody Rituximab, pure or mixed with other proteins, demonstrates the scope of the Lys-His tag acylation method.
KW - acylation
KW - antibodies
KW - chemical biology
KW - peptide tags
KW - site-selective protein modification
U2 - 10.1002/chem.202200147
DO - 10.1002/chem.202200147
M3 - Journal article
C2 - 35099088
AN - SCOPUS:85124710898
VL - 28
JO - Chemistry: A European Journal
JF - Chemistry: A European Journal
SN - 0947-6539
IS - 15
M1 - e202200147
ER -
ID: 299399919