Abstract:
:Pyrroline-carboxy-lysine (Pcl) is a demethylated form of pyrrolysine that is generated by the pyrrolysine biosynthetic enzymes when the growth media is supplemented with D-ornithine. Pcl is readily incorporated by the unmodified pyrrolysyl-tRNA/tRNA synthetase pair into proteins expressed in Escherichia coli and in mammalian cells. Here, we describe a broadly applicable conjugation chemistry that is specific for Pcl and orthogonal to all other reactive groups on proteins. The reaction of Pcl with 2-amino-benzaldehyde or 2-amino-acetophenone reagents proceeds to near completion at neutral pH with high efficiency. We illustrate the versatility of the chemistry by conjugating Pcl proteins with poly(ethylene glycol)s, peptides, oligosaccharides, oligonucleotides, fluorescence, and biotin labels and other small molecules. Because Pcl is genetically encoded by TAG codons, this conjugation chemistry enables enhancements of the pharmacology and functionality of proteins through site-specific conjugation.
journal_name
Proc Natl Acad Sci U S Aauthors
Ou W,Uno T,Chiu HP,Grünewald J,Cellitti SE,Crossgrove T,Hao X,Fan Q,Quinn LL,Patterson P,Okach L,Jones DH,Lesley SA,Brock A,Geierstanger BHdoi
10.1073/pnas.1105197108subject
Has Abstractpub_date
2011-06-28 00:00:00pages
10437-42issue
26eissn
0027-8424issn
1091-6490journal_volume
108pub_type
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