Development of Atroposelective Antibodies by Immunization with a Racemic Mixture of Binaphthyl Derivatives

Abstract

Abstract The design and creation of chiral recognition elements are important for the synthesis, separation, and detection of chiral molecules. We prepare monoclonal antibodies (mAbs), which are chemically homogeneous antibodies, as tailored chiral recognition elements by immunizing mice with a racemic mixture of a binaphthyl derivative (BN (rac)) conjugated to keyhole limpet hemocyanin (KLH). Immunization with BN (rac) induces an immunoresponse that is as strong as that with enantiomerically pure antigens and yields mAbs for each enantiomer of BN, simultaneously. Notably, one of the mAbs prepared by immunization with BN (rac) recognizes the axial chirality of the BN enantiomer with a 14000-fold difference in affinity. These findings provide a strategy to obtain atroposelective antibodies for each enantiomer of BN with a single immunization. mAbs also recognize the axial chirality of 1,1′-bi-2-naphthol (BINOL) and 1,1′-binaphthyl-2,2′-diyl hydrogen phosphate (BNPA), which are an important chiral building block and a chiral organic catalyst, respectively. The cross reactivity of mAbs for the partial structure of BN is significantly low. Therefore, mAbs recognize the axial chirality of BN, BINOL, and BNPA by binding their binaphthyl moiety.