Bioconjugation of Captopril-Light Subunit of Agaricus bisporus Mushroom Tyrosinase: characterization and potential use as a drug carrier for oral delivery

Abstract

We show that a lectin like protein from the mushroom Agaricus bisporus (LSMT) is capable to permeate the epithelial monolayer barrier of the intestine ex vivo. The protein is not toxic or immunogenic upon prolonged administration and elevated dose in mice. Thus, it could be a candidate as a drug carrier for oral administration. However, its permeability should be tested after the protein has been modified, mimicking the condition in which it is used as a drug carrier. The protein was conjugated to captopril, the selected model of a BCS class III drug, with high solubility but poor permeability. The drug was conjugated to LSMT that had been modified with SMPT as a linker. The success of LSMT modification was confirmed with thin layer chromatography and mass spectrometry; the latter also indicated the amount of captopril molecule linked. The modified LSMT could permeate through the intestinal monolayer barrier, and thus could be absorbed in the intestine after modification. The modified protein appears to remain stable after incubation in simulated gastrointestinal fluids. This pioneering work provides an essential basis for further development of the protein as a drug carrier for oral administration.