Boron to be wild…

The ability to efficiently deliver cargo into living cells is a cornerstone of advancements across chemistry, biology, and medicine. From gene therapy to drug delivery, the potential applications are vast. Cell-penetrating peptides (CPPs) have emerged as promising tools for this purpose, offering a relatively non-invasive method for transporting molecules across cellular membranes. However, optimizing CPPs for specific applications often requires enhancing their delivery efficiency and targeting capabilities. One strategy involves the conjugation of additional functional units, such as boronic acid modules, which can interact with cell surface glycans to facilitate internalization. The Bioorganic Synthesis Group (Oliver Seitz) investigated the potential of boronic acid conjugation to transform non-CPP peptides into functional delivery vehicles. If you want to know more about boronic acid-mediated CPPs and their potential for targeted cellular delivery, check out their Chembiochem: a European journal of chemical biology Article!

Abstract

Delivering cargo into live cells has extensive applications in chemistry, biology, and medicine. Cell-penetrating peptides (CPPs) provide an ideal solution for cellular delivery. Enhancing CPPs with additional functional units can improve delivery efficiency. We investigate the conjugation of boronic acid modules to enhance internalization through interactions with cell surface glycans. The aim of this study is to determine whether adding boronic acid can transform a peptide that typically lacks CPP properties into one that functions as a CPP, enabling the delivery of crucial biological cargo like ubiquitin (Ub). The zinc finger protein in its apo state was selected as a “boronate-enabled” CPP. Results indicate that skeletal point mutations and post-synthetic modifications, combined with conjugated benzoboroxole derivatives, enable the apo-ZFP the ability to transport Ub within A549 cells, confirmed through microscopy and flow cytometry. This effective internalization of cargo offers valuable insights for advancing the development of boronic acid-mediated cell-penetrating peptides.