Monoclonal antibodies to lipophilic and short-sized haptens: Application to the 4-amino-quinoline antimalarial drugs

Abstract Monoclonal antibodies recognizing the 4-amino-7-chloro-quinoline (ACQ) structure, which represents the backbone of the 4-amino-quinoline antimalarial drugs, were obtained in mice, after injection of ACQ coupled to hemocyanin via the glutaraldehyde method. The resulting antibodies show a definite specificity to this hapten, but react better with compounds substituted on the exocyclic amino group in 4. It is postulated that the quinoline ring is not sufficient for the reaction with the antibodies, and that an enlarged structure, which is given by the bridge used to link hapten and carrier, entails an important increase (1000-fold) in the apparent affinity. The striking similarities between this bridge and the lateral chains of the antimalarial drugs are accountable for this enhanced recognition. This result allows us to indicate that in some instances, the bridge-structure of the immunogen should be positively involved in the epitope. This observation may become useful in the conception of immunogens, aiming to obtain antibodies directed against some lipophilic and small-sized haptens.