Reversible Lysine Modification on Proteins by Using Functionalized Boronic Acids

• Published in: Chemistry : a European journal Vol. 21; no. 22; pp. 8182 - 8187
• Main Authors: Cal, Pedro M. S. D., Frade, Raquel F. M., Cordeiro, Carlos, Gois, Pedro M. P.
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 26.05.2015; WILEY‐VCH Verlag; Wiley; Wiley Subscription Services, Inc
• Subjects: Acids; Alkynes - chemistry; Animals; Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - pharmacology; Azides - chemistry; boronic acids; Boronic Acids - chemistry; Cell Line; Cell Line, Tumor; Chemistry; Chemistry, Multidisciplinary; Conjugates; conjugation; cycloaddition; drug design; Drugs; Folic acid; Folic Acid - chemistry; Fructose; Humans; Imines - chemistry; Insulin - chemistry; Lysine; Lysine - chemistry; Models, Molecular; Muramidase - chemistry; Neoplasms - drug therapy; Paclitaxel - chemistry; Paclitaxel - pharmacology; Physical Sciences; Polyethylene glycol; Polyethylene Glycols - chemistry; protein modifications; Proteins; Proteins - chemistry; Science & Technology; Strategy; cycloaddition; protein modifications; drug design; CHEMISTRY; conjugation; CANCER; boronic acids
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201500127

Iminoboronates have been utilized to successfully install azide and alkyne bioorthogonal functions on proteins, which may then be further reacted with their bioorthogonal counterparts. These constructs were also used to add polyethylene glycol (PEG) to insulin, a modification which has been shown to be reversible in the presence of fructose. Finally, iminoboronates were used to assemble a folic acid/paclitaxel small‐molecule/drug conjugate in situ with an IC50 value of 20.7 nM against NCI‐H460 cancer cells and negligible cytotoxicity against the CRL‐1502 noncancer cells. Easy installation: The use of iminoboronates is a successful strategy to install diverse functions on proteins (see picture; GSH=glutathione, PEG=polyethylene glycol) and to assemble a folic acid/paclitaxel small‐molecule/drug conjugate in situ.