Meta-Tyrosine Conjugates Labeled 64Cu and 68Ga as A Cancer Radiodiagnosis Agent using Molecular Docking Simulation on LAT-1

Objective: This in silico study aims to determine the most potential compound of meta-tyrosine (JX-075, JX-078, and JX-119)64Cu and68Ga conjugated with various bifunctional chelating agents, NOTA, DOTA, and NODAGA, against the antiporter site of the LAT1 as conduct to develop a cancer diagnostic compound. Methods: Molecular docking simulation was performed to investigate the interactions between meta-tyrosine compounds and LAT-1. Ligand compounds were drawn in 2D structures using ChemDraw Professional 16.0 and then labeled with64 Cu and68Ga to build a radiopharmaceutical scaffold. The docking process was validated, characterized, and evaluated the interaction using several docking protocols in MOE 2020, a license owned by Gadjah Mada University. A visualization of the protein with the ligand was carried out on the BIOVIA Discovery Studio 2020. Results: Docking simulation results show that JX119 has greater potential due to lower bond energy, JX119NODAGA68Ga of-9.22 kcal/mol and JX119NODAGA64Cu of-9.09 kcal/mol. This compound showed interactions with transporter amino acid sites Tyr259 and Phe252, both JX-119NODAGA68 Ga and JX119NODAGA64Cu. Conclusion: The compounds 64CuCu-NODAGA-JX119 and 68GaGa-NODAGA-JX119 are the most potential compounds with the lowest (most negative) Gibbs energy as conduct to develop a diagnostic compound.