Dendronylation: Residue-specific chemoselective attachment of oligoglycerol dendrimers on proteins with noncanonical amino acids.
Polyglycerol dendrimers as an important class of polymeric materials especially attractive for covalent attachment to therapeutic proteins as a useful alternative to traditional PEGylation procedures. Herein, we combine in vivo noncanonical amino acid (ncAA) incorporation and chemoselective conjugation in vitro to produce novel hybrid protein-dendrimer conjugates with the defined architectures. We incorporated Azidohomoalanine (Aha) as methionine substitute in vivo into various protein scaffolds to allow non-invasive dendrimer conjugations (dendronylation). Our approach makes recombinant proteins accessible for the design of multivalent dendrimer conjugates since it enables the preparation of many sequences with various positions for regioselective dendronylation.
Technische Universität Berlin, Institut für Chemie, Müller-Breslau Str. 10, 10623 Berlin, Germany.
Ying
Y
Ma
Freie Universität Berlin, Berlin, Institut für Chemie und Biochemie, Takustrasse 3, 14195 Berlin, Germany.
Bala N S
BN
Thota
Freie Universität Berlin, Berlin, Institut für Chemie und Biochemie, Takustrasse 3, 14195 Berlin, Germany. Electronic address: haag@chemie.fu-berlin.de.
Rainer
R
Haag
Technische Universität Berlin, Institut für Chemie, Müller-Breslau Str. 10, 10623 Berlin, Germany. Electronic address: nediljko.budisa@tu-berlin.de.
Nediljko
N
Budisa
D000409:Alanine / Q000031:analogs & derivatives / Q000378:metabolism; D019943:Amino Acid Substitution; D001386:Azides / Q000737:chemistry; D001407:Bacillus / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D057930:Click Chemistry; D050091:Dendrimers / Q000138:chemical synthesis* / Q000737:chemistry; D004926:Escherichia coli; D005990:Glycerol / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D008715:Methionine / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
D001386:Azides; D001426:Bacterial Proteins; D050091:Dendrimers; D011994:Recombinant Proteins; C506098:azidohomoalanine; C057438:barstar protein, Bacillus amyloliquefaciens; D008715:Methionine; D000409:Alanine; D005990:Glycerol
Click-chemistry; Noncanonical amino acids; Oligoglycerol dendrons; Protein–dendron conjugate; Unnatural protein expression