A new analogue of islet neogenesis associated protein with higher structural and plasma stability

Abstract

Islet Neogenesis Associated Protein pentadecapeptide (INGAP-PP) increases β-cell mass and function in experimental animals. A short clinical trial also yielded promising results. However, HTD4010, a new peptide derived from INGAP-PP, was developed in order to optimize its specific effects by minimizing its side effects. To study and compare the tertiary structure, stability dynamics, and plasma stability of HTD4010, an INGAP-PP analogue. Both peptides were pre-incubated in human, rat and mouse plasma at 37 °C, and their presence was identified and quantified by high performance liquid chromatography at different time-points. GROMACS 2019 package and the Gromos 54A7 force field were used to evaluate overall correlated motion of the peptide molecule during molecular dynamics simulation by essential dynamics. HTD4010 exhibited significantly larger plasma stability than INGAP-PP, and its structural stability was almost 3.36-fold higher than INGAP-PP. These results suggest that HTD4010 may facilitate longer tissue interaction, thereby developing higher potential biological effects. If so, HTD4010 may become a promising therapeutic agent to treat people with diabetes. Communicated by Ramaswamy H. Sarma.