Evaluation of Ethyl Acetate as a Dichloromethane Replacement in Solid-Phase Peptide Synthesis of pHLIP

Author: Nilia Francis

Field of Study: Biochemistry; Global Public Health

Program Affiliation: McNair Scholars Program

Faculty Mentors: Ming An

Easel: 64

Timeslot: Afternoon

Abstract: The pH-low insertion peptide (pHLIP) is currently being investigated as an imaging agent or a peptide-drug conjugate targeting cancer cells based on tumor acidosis. We are investigating the lipidation of pHLIP as a way to improve its properties, which requires its synthesis using resin-based solid-phase peptide synthesis (SPPS). Dichloromethane (DCM) is used during SPPS as a resin swelling and washing solvent. However, DCM has carcinogenic properties and is being phased out as a SPPS solvent. Ethyl acetate (EtOAc) is more environmentally friendly and less toxic than DCM. The goal of this project was to test the synthesis of a pHLIP variant using EtOAc as a substitute. The yield decreased by 2% (9% for EtOAc vs. 11% for DCM) while the purity of the crude decreased by 3% (13% for EtOAc vs. 16% for DCM). Therefore, my results suggest that EtOAc is an acceptable replacement for DCM in SPSS of pHLIP.