PEGylation and Dimerization of Expressed Proteins under Near Equimolar Conditions with Potassium 2-Pyridyl Acyltrifluoroborates

Open access
Date
2018-02Type
- Journal Article
Citations
Cited 40 times in
Web of Science
Cited 40 times in
Scopus
ETH Bibliography
yes
Altmetrics
Abstract
The covalent conjugation of large, functionalized molecules remains a frontier in synthetic chemistry, as it requires rapid, chemoselective reactions. The potassium acyltrifluoroborate (KAT)–hydroxylamine amide-forming ligation shows promise for conjugations of biomolecules under aqueous, acidic conditions, but the variants reported to date are not suited to ligations at micromolar concentrations. We now report that 2-pyridyl KATs display significantly enhanced ligation kinetics over their aryl counterparts. Following their facile, one-step incorporation onto the termini of polyethylene glycol (PEG) chains, we show that 2-pyridyl KATs can be applied to the construction of protein–polymer conjugates in excellent (>95%) yield. Four distinct expressed, folded proteins equipped with a hydroxylamine could be PEGylated with 2–20 kDa 2-pyridyl mPEG KATs in high yield and with near-equimolar amounts of coupling partners. Furthermore, the use of a bis 2-pyridyl PEG KAT enables the covalent homodimerization of proteins with good conversion. The 2-pyridyl KAT ligation offers an effective alternative to conventional protein–polymer conjugation by operating under aqueous acidic conditions well suited for the handling of folded proteins. Show more
Permanent link
https://doi.org/10.3929/ethz-b-000249993Publication status
publishedExternal links
Journal / series
ACS Central ScienceVolume
Pages / Article No.
Publisher
American Chemical SocietyOrganisational unit
03861 - Bode, Jeffrey W. / Bode, Jeffrey W.
Funding
154460 - Novel biological and therapeutic mechanisms to enhance brown adipocyte formation and function (SNF)
More
Show all metadata
Citations
Cited 40 times in
Web of Science
Cited 40 times in
Scopus
ETH Bibliography
yes
Altmetrics