Side-chain cysteine-functionalized poly(2-oxazoline)s for multiple peptide conjugation by native chemical ligation.
We prepared statistical copolymers composed of 2-methyl-2-oxazoline (MeOx) in combination with 2-butenyl-2-oxazoline (BuOx) or 2-decenyl-2-oxazoline (DecOx) as a basis for polymer analogous introduction of 1,2-aminothiol moieties at the side chain. MeOx provides hydrophilicity as well as cyto- and hemocompatibility, whereas the alkene groups of BuOx and DecOx serve for functionalization with a thiofunctional thiazolidine by UV-mediated thiol-ene reaction. After deprotection the cysteine content in functionalized poly(2-oxazoline) (POx) is quantified by NMR and a modified trinitrobenzenesulfonic acid assay. The luminescent cell viability assay shows no negative influence of cysteine-functionalized POx (cys-POx) concerning cell viability and cell number. cys-POx was used for multiple chemically orthogonal couplings with thioester-terminated peptides through native chemical ligation (NCL), which was performed and confirmed by NMR and MALDI-ToF measurements.
†Department of Functional Materials in Medicine and Dentistry, University of Würzburg, Pleicherwall 2, 97070 Würzburg, Germany.
Michael
M
Schmitz
†Department of Functional Materials in Medicine and Dentistry, University of Würzburg, Pleicherwall 2, 97070 Würzburg, Germany.
Matthias
M
Kuhlmann
‡Department Chemical Biology II, Leibniz-Institut für Molekulare Pharmakologie (FMP), Robert-Rössle-Straße 10, 13125 Berlin, Germany.
Oliver
O
Reimann
‡Department Chemical Biology II, Leibniz-Institut für Molekulare Pharmakologie (FMP), Robert-Rössle-Straße 10, 13125 Berlin, Germany.|§Humboldt Universität zu Berlin, Department Chemie, Brook-Taylor-Straße 2, 12489 Berlin, Germany.
Christian P R
CP
Hackenberger
†Department of Functional Materials in Medicine and Dentistry, University of Würzburg, Pleicherwall 2, 97070 Würzburg, Germany.
Jürgen
J
Groll
D002460:Cell Line; D002470:Cell Survival; D003545:Cysteine / Q000737:chemistry*; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D010080:Oxazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D010455:Peptides / Q000737:chemistry; D011073:Polyamines / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity
D010080:Oxazoles; D010455:Peptides; D011073:Polyamines; C117403:poly(2-methyl-2-oxazoline); C577913:poly(2-oxazoline); D003545:Cysteine