title: Reversible lysine modification on proteins by using functionalized boronic acids.
abstract: 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.
authors.affiliation: Research Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, 1649-003 Lisbon (Portugal), Fax: (+351) 217946470.
authors.forename: Pedro M S D
authors.initials: PM
authors.lastname: Cal
authors.affiliation: Research Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, 1649-003 Lisbon (Portugal), Fax: (+351) 217946470.
authors.forename: Raquel F M
authors.initials: RF
authors.lastname: Frade
authors.affiliation: Chemistry and Biochemistry Centre, Faculty of Science, University of Lisbon, 1749-016 Lisbon (Portugal).
authors.forename: Carlos
authors.initials: C
authors.lastname: Cordeiro
authors.affiliation: Research Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, 1649-003 Lisbon (Portugal), Fax: (+351) 217946470. pedrogois@ff.ulisboa.pt.
authors.forename: Pedro M P
authors.initials: PM
authors.lastname: Gois
mesh_terms: D000480:Alkynes / Q000737:chemistry; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology; D001386:Azides / Q000737:chemistry; D001897:Boronic Acids / Q000737:chemistry*; D002460:Cell Line; D045744:Cell Line, Tumor; D005492:Folic Acid / Q000737:chemistry; D006801:Humans; D007097:Imines / Q000737:chemistry; D007328:Insulin / Q000737:chemistry; D008239:Lysine / Q000737:chemistry*; D008958:Models, Molecular; D009113:Muramidase / Q000737:chemistry; D009369:Neoplasms / Q000188:drug therapy; D017239:Paclitaxel / Q000737:chemistry / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000737:chemistry; D011506:Proteins / Q000737:chemistry*
chemical_list: D000480:Alkynes; D000972:Antineoplastic Agents, Phytogenic; D001386:Azides; D001897:Boronic Acids; D007097:Imines; D007328:Insulin; D011506:Proteins; D011092:Polyethylene Glycols; D005492:Folic Acid; D009113:Muramidase; D008239:Lysine; D017239:Paclitaxel
keywords: boronic acids; conjugation; cycloaddition; drug design; protein modifications