Effects of serum albumin on SPR-measured affinity of small molecule inhibitors binding to nerve growth factor

Abstract

The study of the interactions between a drug and plasma serum proteins are necessary in determining pharmacological and toxicological properties for therapeutic development. Small molecule nerve growth factor (NGF) inhibitors have been investigated for their abilities to inhibit NGF binding to TrkA as a potential therapeutic option for the treatment of neuropathic and inflammatory pain. In this study, surface plasmon resonance (SPR) spectroscopy and 125I-NGF radioisotope binding assays were carried out to better understand the role of serum albumin (SA) in small molecule binding to NGF. SA has been characterized as a universal drug carrier with up to seven binding domains on its surface to transport drug molecules to target tissues. Here, we use SPR kinetic analysis to analyze the change in specificity of small molecules to immobilized NGF in the presence and absence of SA. In the presence of SA an overall increase in small molecule binding affinity for NGF was observed compared to binding in the absence of SA. Our results suggest a crucial role for SA in the pharmacokinetics of small molecule binding to NGF. This effect will require consideration when developing therapeutic agents.