The role of peptide composition and architecture for folic acid delivery, and evaluation of anti-inflammatory properties

Abstract

Folate is an essential component of many metabolic processes, including the synthesis of nucleoproteins, purines, and pyrimidines, and is a recommended supplement to lower the incidence of various disorders, including neural tube birth defect formation. Folate metabolism involving one-carbon (1C) transfer processes, requires folate in the form of a cofactor, which contributes to the production of the amino acids, methionine, DNA nucleotides, and is involved in controlling blood homocysteine levels that ultimately impact immunomodulatory profiles of host’s immune system. Given the key role of folate in immunomodulation, the purpose of this study specifically focuses on uptake mechanism of folate in immune and gastric cells, its effect on folic acid receptors and extracellularly in the gastrointestinal tract, on the role of folic acid (synthetic form of folate) in inflammation and immunomodulation. In this study a library of cell penetrating peptides (CPP) was developed using their linear and cyclic versions folic acid conjugations. Further, the CPP conjugates were tested against cell viability and cell penetration followed by their effects on the folic acid receptor. CPP conjugates showed successful cellular uptake by using fluorophore (TAMRA), the study also confirmed the folic acid internalisation by downregulation of folic acid receptors suggesting the saturation of folic acid inside the cell. One of the main events folic acid undergoes after internalisation is its conversion into dihydrofolate and tetrahydrofolate by the enzyme dihydro folate reductase (DHFR), which was demonstrated from DHFR assay for further confirmation of results. The biomedical applications of CPPs are extensively studied, including their potential in delivering imaging agents, antimicrobial and antifungal actions, anti-inflammatory activity, and tumor therapy