Synthesis and Characterization of Phenylboronic Acid-Modified Insulin With Glucose-Dependent Solubility

Nai-Pin Lin; Nan Zheng; Landa Purushottam; Yi Wolf Zhang; Danny Hung-Chieh Chou

doi:10.3389/fchem.2022.859133

Synthesis and Characterization of Phenylboronic Acid-Modified Insulin With Glucose-Dependent Solubility

Front Chem. 2022 Mar 16:10:859133. doi: 10.3389/fchem.2022.859133. eCollection 2022.

Authors

Nai-Pin Lin^{1

2}, Nan Zheng², Landa Purushottam¹, Yi Wolf Zhang^{1

2}, Danny Hung-Chieh Chou^{1

2}

Affiliations

¹ Department of Pediatrics, Division of Diabetes and Endocrinology, Stanford University, Stanford, CA, United States.
² Department of Biochemistry, University of Utah, Salt Lake City, UT, United States.

Abstract

Glucose-responsive insulin represents a promising approach to regulate blood glucose levels. We previously showed that attaching two fluorophenylboronic acid (FPBA) residues to the C-terminal B chain of insulin glargine led to glucose-dependent solubility. Herein, we demonstrated that relocating FPBA from B chain to A chain increased the baseline solubility without affecting its potency. Furthermore, increasing the number of FPBA groups led to increased glucose-dependent solubility.

Keywords: glucose responsiveness; insulin; insulin modification; peptide; phenylboronate.

Grants and funding

R01 DK121336/DK/NIDDK NIH HHS/United States