Design and Development of a Novel Peptide Theranostic Agent

Abstract

Theranostic agents are compounds that combine both therapeutic and diagnostic functionalities for monitoring and treatment in real time. Peptides exhibit favorable properties such as high affinity to protein targets and ability to be modified, and are therefore good candidates for the design of theranostic agents. This study investigates the physical and chemical properties of a novel peptide, HFS_Gluc, which is designed to serve as a theranostic agent of sodium-glucose cotransporter 2 (SGLT2), a protein overexpressed in various tumor cells. This peptide aims to mimic the affinity of the SGLT2 inhibitor, empagliflozin, without exhibiting the negative effects empagliflozin has shown in other studies. The physical properties of the HFS_Gluc peptide were assessed via solubility and stability tests across a range of pH values and buffers. Metal binding affinity assays assess the ability of the peptide to bind to copper ions, essential for imaging and therapeutic purposes. pH tests, quantified by MALDI-MS, indicate that HFS_Gluc shows little to no water solubility, tested over a broad pH range (4.4-8.3) using different buffers (HEPES 50 mM, MES 50 mM, and CHES 50 mM). Preliminary computational data using AutoDock shows HDS_Gluc as an alternative candidate (-11.2 kcal/mol vs. -9.91 kcal/mol). This peptide was synthesized using Solid Phase Peptide Synthesis and is currently being tested for solubility and metal binding. If solubility and stability shows improvement compared to the previous peptide candidate, HDS_Gluc can possibly be used in the imaging and treatment of cancers linked with overexpression of SGLT2.