用丙酮酰化人型复合寡糖修饰的荧光白蛋白的体内成像揭示了类似唾液酸化的生物分布和动力学。

In vivo imaging of fluorescent albumin modified with pyruvylated-human-type complex oligosaccharide reveals sialylation-like biodistribution and kinetics.

作者信息

Fukuhara Ryoichiro, Ogura Akihiro, Yoshinaga Sho, Fukunaga Takamasa, Kinoshita Takashi, Sumiyoshi Wataru, Higuchi Yujiro, Tanaka Katsunori, Takegawa Kaoru

机构信息

Department of Bioscience and Biotechnology, Faculty of Agriculture, Kyushu University, 744 Motooka, Fukuoka 819-0395, Japan.

Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan.

出版信息

Bioorg Med Chem. 2022 Sep 15;70:116943. doi: 10.1016/j.bmc.2022.116943. Epub 2022 Jul 22.

DOI:10.1016/j.bmc.2022.116943

PMID:35905685

Abstract

Both pyruvylation and sialylation onto the terminus of oligosaccharides of N-glycoproteins seem to be structurally and functionally similar with a property of conferring negative charge. However, detailed molecular characteristics of pyruvylation and sialylation in vivo were elusive. Here, to investigate an effect of terminal pyruvylation to N-glycan on in vivo biodistribution and kinetics, we prepared human serum albumin (HSA) modified with pyruvylated N-glycan (PvG), conjugated with HiLyte Fluor 750 (FL750-PvGHSA). In vivo imaging by using FL750-PvGHSA revealed that terminally pyruvylated N-glycoalbumin was excreted like sialylated N-glycoalbumin, suggesting that pyruvylation mimics sialylation in in vivo biodistribution and kinetics of N-glycoproteins. Terminal pyruvylation onto N-glycans can be a potential tool for a novel glycoengineering strategy.

摘要

N-糖蛋白寡糖末端的丙酮酰化和唾液酸化在结构和功能上似乎相似，都具有赋予负电荷的特性。然而，体内丙酮酰化和唾液酸化的详细分子特征尚不清楚。在此，为了研究N-聚糖末端丙酮酰化对体内生物分布和动力学的影响，我们制备了用丙酮酰化N-聚糖（PvG）修饰的人血清白蛋白（HSA），并与HiLyte Fluor 750（FL750-PvGHSA）偶联。使用FL750-PvGHSA进行的体内成像显示，末端丙酮酰化的N-糖基化白蛋白像唾液酸化的N-糖基化白蛋白一样被排泄，这表明丙酮酰化在N-糖蛋白的体内生物分布和动力学方面模拟了唾液酸化。N-聚糖的末端丙酮酰化可能是一种新型糖工程策略的潜在工具。