Work

Discovery of a Cyclic Cell-Penetrating Peptide with Improved Endosomal Escape and Cytosolic Delivery Efficiency

Year: 2022

Type: article

Abstract: Cyclic cell-penetrating peptide 12 (CPP12) is highly efficient for the cytosolic delivery of a variety of cargo molecules into mammalian cells in vitro and in vivo. However, its cytosolic entry efficiency is substantially reduced at lower concentrations or in the presence of serum proteins. In this study, CPP12 analogs were prepared by replacing its hydrophobic residues with amino acids of varying hydrophobicity and evaluated for cellular entry. Substitution of l-3-benzothienylalanine (Bta) for l-2-naphthylalanine (Nal) resulted in CPP12-2, which exhibits up to 3.8-fold higher cytosolic entry efficiency than CPP12, especially at low CPP concentrations; thanks to improved endosomal escape efficiency. CPP12-2 is well suited for the cytosolic delivery of highly potent cargos to achieve biological activity at low concentrations.

Source: Molecular Pharmaceutics

DOI: 10.1021/acs.molpharmaceut.1c00924

Authors: Marina Buyanova, Ashweta Sahni, Rui Yang, Amar Sarkar, Heba Salim, Dehua Pei

Institution: The Ohio State University

Language: English

Topic: RNA Interference and Gene Delivery

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: Entrada Therapeutics, National Cancer Institute, National Institute of General Medical Sciences