title: Molecularly imprinted tunable binding sites based on conjugated prosthetic groups and ion-paired cofactors.
abstract: A molecular imprinting technique was applied to the construction of prosthetic group-coupled tunable binding cavities for bisphenol A (BPA). A novel template molecule, with a structure consisting of BPA covalently conjugated with two allyl(4-carboxyphenyl)disulfides through ester bonds (BPA-D), was designed. After copolymerization of BPA-D with styrene and divinylbenzene, the BPA di(4-mercaptobenzoate) moieties were removed by reductive cleavage of the disulfide bonds, resulting in apo-type molecularly imprinted cavities bearing two thiol residues. 4-Mercaptobenzoic acid was introduced into the apo-type cavities as a prosthetic group through a disulfide bond by addition of 4,4'-dithiodibenzoic acid, which transformed the apo-type cavities into holo-type cavities with two carboxylic acid residues for binding BPA. When pyridyl prosthetic groups were introduced instead of 4-mercaptobenzoic acid by using 4,4'-dithiodipyridine, BPA recognition ability was maintained but with improved selectivity. The binding affinity was successfully altered several times by attaching and detaching these prosthetic groups, which showed that the apo-type scaffold could be reused. Furthermore, noncovalent-type ion-paired cofactors could be introduced, when the two thiol groups in the apo-type cavities were oxidized to sulfonic acid groups. When 1,2-diaminoethane (DAE) was added to the oxidized apo-type scaffold as a noncovalent-type cofactor, the binding activity was regulated successively, depending upon the concentrations of DAE added. By using various prosthetic groups and cofactors, the binding properties of the holo-type cavities could be tuned in a similar way to those found in biological systems.
authors.affiliation: Graduate School of Engineering, Kobe University, Nada-ku, Kobe 657-8501, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Takeda
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kuwahara
authors.forename: Kohei
authors.initials: K
authors.lastname: Ohmori
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Takeuchi
mesh_terms: D001559:Benzhydryl Compounds; D001565:Benzoates / Q000737:chemistry; D001665:Binding Sites; D004220:Disulfides / Q000737:chemistry; D005029:Ethylenediamines / Q000737:chemistry; D054802:Molecular Imprinting / Q000379:methods*; D015394:Molecular Structure; D010636:Phenols / Q000737:chemistry*; D011725:Pyridines / Q000737:chemistry; D013438:Sulfhydryl Compounds / Q000737:chemistry; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D001565:Benzoates; D004220:Disulfides; D005029:Ethylenediamines; D010636:Phenols; D011725:Pyridines; D013438:Sulfhydryl Compounds; C543486:4,4'-dithiodibenzoic acid; C013594:4-mercaptobenzoate; C007542:4,4'-dipyridyl disulfide; C031234:ethylenediamine; C006780:bisphenol A; D000098826:Bisphenol A Compounds