Reversible Lysine Modification on Proteins by Using Functionalized Boronic Acids

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...

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Bibliographic Details
Published in:Chemistry : a European journal 2015-05, Vol.21 (22), p.8182-8187
Main Authors: Cal, Pedro M. S. D., Frade, Raquel F. M., Cordeiro, Carlos, Gois, Pedro M. P.
Format: Article
Language:English
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
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
Polyethylene glycol
Polyethylene Glycols - chemistry
protein modifications
Proteins
Proteins - chemistry
Strategy
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Summary: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.
ISSN:0947-6539
1521-3765
DOI:10.1002/chem.201500127