title: Revisiting Boronate/Diol Complexation as a Double Stimulus-Responsive Bioconjugation.
abstract: This study presents a quantitative assessment of the complexation between boronic acids and diols as a reversible and double-stimulus (oxidation and acidification)-responsive bioconjugation reaction. First, by using a competition assay, we have evaluated the equilibrium constants (water, pH 7.4) of 34 boronate/diol pairs, using diols of both aliphatic and aromatic (catechols) nature; in general, catechols were characterized by constants 3 orders of magnitude higher than those of aliphatic diols. Second, we have demonstrated that successful complexation with diols generated in situ via enzymatic reactions, and the boronate complexation was also employed to calculate the Michaelis-Menten parameters for two catechol-producing reactions: the demethylation of 3-methoxytyramine and the 2-hydroxylation of estradiol, respectively, mediated by P4502D6 and P4501A2. Third, we have prepared phenylboronic acid-functionalized hyaluronic acid (HA) and demonstrated the pH and H2O2-responsive character of the adducts that it formed with Alizarin Red S (ARS) used as a model catechol. The versatility and selectivity of the complexation and the mild character of the chemical species involved therefore make the boronate/catechol reaction an interesting candidate for bioconjugation purposes.
authors.affiliation: NorthWest Centre of Advanced Drug Delivery (NoWCADD), School of Health Sciences, University of Manchester , Oxford Road, Manchester, M13 9PT, United Kingdom.
authors.forename: Arianna
authors.initials: A
authors.lastname: Gennari
authors.affiliation: NorthWest Centre of Advanced Drug Delivery (NoWCADD), School of Health Sciences, University of Manchester , Oxford Road, Manchester, M13 9PT, United Kingdom.
authors.forename: Chirag
authors.initials: C
authors.lastname: Gujral
authors.affiliation: NorthWest Centre of Advanced Drug Delivery (NoWCADD), School of Health Sciences, University of Manchester , Oxford Road, Manchester, M13 9PT, United Kingdom.
authors.forename: Erwin
authors.initials: E
authors.lastname: Hohn
authors.affiliation: NorthWest Centre of Advanced Drug Delivery (NoWCADD), School of Health Sciences, University of Manchester , Oxford Road, Manchester, M13 9PT, United Kingdom.
authors.forename: Enrique
authors.initials: E
authors.lastname: Lallana
authors.affiliation: Dipartimento di Chimica, Materiali ed Ingegneria Chimica "G. Natta", Politecnico di Milano , Via Mancinelli 7, 20131 Milan, Italy.|Fondazione CEN - European Centre for Nanomedicine , Piazza Leonardo da Vinci 32, 20133 Milan, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Cellesi
authors.affiliation: NorthWest Centre of Advanced Drug Delivery (NoWCADD), School of Health Sciences, University of Manchester , Oxford Road, Manchester, M13 9PT, United Kingdom.
authors.forename: Nicola
authors.identifier: 0000-0002-4879-3949
authors.initials: N
authors.lastname: Tirelli
mesh_terms: D000880:Anthraquinones / Q000737:chemistry* / Q000378:metabolism; D001897:Boronic Acids / Q000737:chemistry* / Q000378:metabolism; D002396:Catechols / Q000737:chemistry* / Q000378:metabolism; D002846:Chromatography, Affinity; D004298:Dopamine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D004958:Estradiol / Q000737:chemistry* / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000737:chemistry / Q000378:metabolism; D010084:Oxidation-Reduction; D014867:Water / Q000737:chemistry / Q000378:metabolism
chemical_list: D000880:Anthraquinones; D001897:Boronic Acids; D002396:Catechols; D014867:Water; C004468:Alizarin Red S; D004958:Estradiol; D006861:Hydrogen Peroxide; C001746:3-methoxytyramine; C010686:benzeneboronic acid; C034221:catechol; D004298:Dopamine