Influence of Small Molecule Property on Antibody Response

TL;DR

This study investigates how the hydrophobicity of small molecules influences antibody response, revealing a positive correlation that can guide the design of better immunogens for vaccines and diagnostics.

Contribution

It demonstrates that small molecule hydrophobicity correlates with antibody titer and affinity, providing new insights into immunogen design.

Findings

Antibody response increases with molecular hydrophobicity.

Chemical descriptors related to hydrophobicity predict antibody response.

Design of small molecules can be optimized for stronger immunogenicity.

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 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.