Center for Translational Biomedical Research, University of North Carolina at Greensboro, North Carolina Research Campus, Kannapolis, North Carolina 28081, United States.
Department of Chemistry & Biochemistry, University of North Carolina at Greensboro, Greensboro, North Carolina 27412, United States.
J Am Soc Mass Spectrom. 2021 Mar 3;32(3):744-752. doi: 10.1021/jasms.0c00443. Epub 2021 Jan 29.
A prolonged hyperglycemic condition in diabetes mellitus results in glycation of plasma proteins. (ε)-Carboxymethyllysine (CML) is a well-known protein advanced glycation end product, and one of its mechanisms of formation is through further oxidation of Amadori compound modified lysine (AML). Unlike enrichment of AML peptides using boronate affinity, biochemical enrichment methods are scarce for comprehensive profiling of CML-modified peptides. To address this problem, we used AML peptide sequence and site of modification as template library to identify and quantify CML peptides. In this study, a parallel reaction monitoring workflow was developed to comprehensively quantify CML modified peptides in Type 1 diabetic subjects' plasma with good and poor glycemic control ( = 20 each). A total of 58 CML modified peptides were quantified, which represented 57 CML modification sites in 19 different proteins. Out of the 58 peptides, five were significantly higher in poor glycemic control samples with the area under the receiver operating characteristic curve ≥0.83. These peptides could serve as promising indicators of glycemic control in Type 1 diabetes management.
糖尿病患者的高血糖状态持续时间长会导致血浆蛋白糖化。（ε）-羧甲基赖氨酸（CML）是一种众所周知的蛋白质晚期糖基化终产物，其形成机制之一是通过进一步氧化阿马多里化合物修饰的赖氨酸（AML）。与使用硼酸盐亲和富集 AML 肽不同，用于全面分析 CML 修饰肽的生化富集方法很少。为了解决这个问题，我们使用 AML 肽序列和修饰位点作为模板库来鉴定和定量 CML 修饰肽。在这项研究中，开发了一种平行反应监测工作流程，以全面定量 1 型糖尿病患者血糖控制良好（= 20 例）和较差（= 20 例）的血浆中的 CML 修饰肽。共定量了 58 个 CML 修饰肽，代表 19 种不同蛋白质中的 57 个 CML 修饰位点。在 58 个肽中，有 5 个在血糖控制较差的样本中明显升高，接受者操作特征曲线下的面积≥0.83。这些肽可作为 1 型糖尿病管理中血糖控制的有前途的指标。
