“MD” method for the precise analysis of the O-acetyl-mannan structure and disclosure of the role in the conformational stability of insulin

• Published in: International journal of biological macromolecules 2024-04, Vol.263 (Pt 2), p.129944-129944, Article 129944
• Main Authors: Yang, Liu, Huang, Jia, Qin, Shihui, Shao, Huiyan, Li, Yanlang, Zhou, Ying, Zi, Chengting, Hu, Jiang-Miao
• Format: Article
• Language: English
• Subjects: Acetyl modification site; Dendrobium devonianum acetyl-mannan (DDAM); Disclosure; Hypoglycemic Agents - pharmacology; Insulin; Insulin thermostability; Mannans; Molecular dynamics; Molecular Dynamics Simulation; Polysaccharides - chemistry
• ISSN: 0141-8130; 1879-0003
• DOI: 10.1016/j.ijbiomac.2024.129944

Among the diversified glycan modifications, acylation is one of the most abundant. This modification could be responsible for many of the properties of glycans, such as structural stability and specificity for biological activity. To obtain better insight into the effects of acetylation of glycans on the structure and thermostability of insulin, it is critical to investigate glycans with a high degree of acetylation. An in-depth study of three functional glycans named acetyl-mannan from Dendrobium devonianum (DDAM) was conducted herein by efficient enzymatic depolymerization, and the effect of glycosidic bonds on acetylation modification sites was studied through a molecular dynamics (MD) method, as well as its positive effect on insulin secretion, glucose uptake, and the thermal stability of tertiary structures in vitro. Further study indicated that DDAMs play a hypoglycemic role by sparking the thermostability of the insulin conformation. The hypoglycemic activity displayed a positive correlation with the degree of acetylation in DDAMs. In this work, through the MD method, we confirmed the structure characteristics of DDAMs and provided accurate data support for the structure-activity relationship analysis. Thus, these findings demonstrated that DDAMs might be an exceptional leading compound for the stability of insulin drug. •Through the MD method, we have determined the optimal location for acetylation and the structure of natural complex glycan.•After treatment with DDAMs, the mechanism of hypoglycemic may be related to the increased thermostability of the insulin.•The SAR results suggest that the hypoglycemic activity shown a positive correlation with the degree of acetylation in DDAMs.