Influence of Small Molecular Property on Antibody Response

Abstract

Antibodies with high titer and affinity to small molecule are critical in the field for the development of vaccines against drugs of abuse, antidotes to toxins and immunoassays for compounds. However, little is known regarding how properties of small molecule per se influence and which chemical descriptor could indicate the degree of the antibody response. Based on our previous study, we designed and synthesized two groups of small molecules, called haptens, with varied hydrophobicities to investigate the relationship between properties of small molecules and antibody response in term of titer and affinity. We found that the magnitude of the antibody response is positively correlated with the degree of molecular hydrophobicity and related chemical descriptors. This study provides insight into the immunological characteristics of small molecules themselves and useful clues to produce high-quality antibodies against small molecules.

Hapten Synthesis and Monoclonal Antibody Preparation for Simultaneous Detection of Albendazole and Its Metabolites in Animal-Origin Food

“…Hapten structure determines the specificity and affinity of the resulting antibody [ 30 ]. To produce the antibody that could recognize ABZs, the characteristic structure of these compounds should be maximumly exposed to immune system.…”

“…Critical molecular descriptors were finally compared as shown in Table 3 . Studies have shown that molecular parameters such as lipid-water partition coefficient (Log P , a widely used measure of hydrophobicity), dipole moments (μ, represents the polarity of molecule, the larger the polarity, the stronger the hydrophilicity), and topological polar surface area (TPSA) of analytes are important factors affecting recognition by antibodies [ 34 , 35 , 36 ], and hydrophobic force was believed to be the main driving force between small molecules and antibody [ 30 , 34 ]. In this study, Log P was found to be positively correlated with antibody affinity.…”

“…It can be seen in Figure 3a that all molecules are well coincided with ABZ, and the RMSD values of the alignments are from 2.3 × 10 −3 of ABZNH2SO2 to 1.3 × 10 −2 of ABZSO2 and fenbendazole (Table 3), demonstrating the extent of the difference of other molecules with ABZ, which agreed with CR data on the whole. It can also be seen in Figure 3a, the substitution of carbon or oxygen atom for sulfur atom in flubendazole (in red), mebendazole (in gray), or oxi- ESP describes the potential energy of a proton placed at a point near the mol As different substituents may affect the electrostatic field, ESP analysis helps to visu spatial regions of molecules and to analyze electrostatic interaction between antibod antigen [30,33]. The ESP calculations displayed on van der Waals surfaces of global lo energy conformation are shown in Figure 3b, positive potential energy is represent red areas around the molecules, of which the maxima were marked as golden glo and these areas are repulsive to a proton, negative potential energy is represented by areas on the molecules with the minima marked as light blue globule, and these are attractive to a proton.…”

“…It is clearly seen Figure 3c that the ESP surface area distribution of molecules in different ESP range ESP describes the potential energy of a proton placed at a point near the molecule. As different substituents may affect the electrostatic field, ESP analysis helps to visualize spatial regions of molecules and to analyze electrostatic interaction between antibody and antigen [30,33]. The ESP calculations displayed on van der Waals surfaces of global lowest energy conformation are shown in Figure 3b, positive potential energy is represented by red areas around the molecules, of which the maxima were marked as golden globule, and these areas are repulsive to a proton, negative potential energy is represented by blue areas on the molecules with the minima marked as light blue globule, and these areas are attractive to a proton.…”

Metabolomics for personalized medicine: the input of analytical chemistry from biomarker discovery to point-of-care tests

“…The challenge to develop assays based on the recognition of metabolites by antibodies firstly lies in the possibility to derive these small chemical molecules, to make them haptens (i.e., to link them covalently to carrier proteins whose role is to provoke/favor the immune response in immunized animals, naturally not immunogenic). In some cases, complex coupling chemistry procedures are necessary to obtain an immunogen [ 157 ]. Furthermore, antibodies of interest have to be selected on their specificity to recognize exclusively the molecule, without recognition of the derived molecule, or of related molecules.…”