Analysis of a novel insulin lisargine at the molecular level using X-ray crystallography and biophysical techniques

Abstract

The structural characterization of insulin analogs is crucial for their clinical applications. In previous study, we developed a novel long-acting insulin analog called insulin lisargine, which exhibits superior sustained-release properties. However, its structure remains unclear and requires thorough investigation. We determined the amino acid sequence of insulin lisargine using mass spectrometry and analyzed its secondary structure using circular dichroism spectroscopy. Furthermore, we employed X-ray crystallography experiments at the Shanghai Synchrotron Radiation Facility to elucidate the crystal structure of the insulin lisargine analog, achieving a resolution of approximately 2.0Å. Comparison with the human insulin structure in the Protein Data Bank revealed structural similarities between the two. These findings suggest promising prospects for the insulin lisargine analog and provide essential foundational information for subsequent drug design and optimization. In summary, we conducted a comprehensive structural study on the insulin lisargine analog, shedding light on its potential applications in the field. The obtained insights pave the way for future drug development and optimization efforts.