Kútvölgyi Katalin, Peleskei Zsófia, Demeter Fruzsina, Barta Roland A, Mándi Attila, Homoki Eszter, Oláh Attila, Hajkó János, Herczeg Mihály, Lisztes Erika
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Debrecen, Egyetem tér 1, H-4032 Debrecen, Hungary.
Doctoral School of Pharmacy, Medical Science Doctoral Council, University of Debrecen, Egyetem tér 1, H-4032 Debrecen, Hungary.
Int J Mol Sci. 2025 Aug 27;26(17):8305. doi: 10.3390/ijms26178305.
Glycosaminoglycans (GAGs) are linear, high molecular weight polydisperse heteropolysaccharides consisting of repeating disaccharide units, which always contain a uronic acid building block (e.g., d-glucuronic acid or l-iduronic acid). Their analogues containing d-mannuronic acid were not known until now. Another important class of the linear negatively charged polisaccharides are alginates, which are also present in the cell surface in the cell wall. They are composed of blocks of 1,4-linked β-d-mannuronic acid and its C-5 epimer α-l-guluronic acid in alternating or random order. Both groups of molecules have significant biological activity (e.g., cell growth inhibitory activity, anti-inflammatory effect, etc.). In the course of our research, we combined the structural characteristics of these two groups of molecules and produced a series of heparan sulphate analogue trisaccharides containing d-mannuronic acid, with a simplified structure, in which α- and β-mannosidic bonds are also found. Since trisaccharides may exert diverse biological effects and alginate derivatives can influence wound healing processes, we investigated the effects of the synthesized compounds on primary human dermal fibroblasts. We found that, when applied at 10 μM, none of the compounds influenced viability or spontaneous collagen production; however, some derivatives exhibited anti-inflammatory activity and suppressed the poly(I:C)-induced release of interleukin 6.
糖胺聚糖（GAGs）是由重复二糖单元组成的线性、高分子量多分散杂多糖，其总是包含一个糖醛酸结构单元（例如，d - 葡萄糖醛酸或l - 艾杜糖醛酸）。直到现在，其含有d - 甘露糖醛酸的类似物还不为人所知。另一类重要的线性带负电荷的多糖是藻酸盐，其也存在于细胞壁的细胞表面。它们由1,4 - 连接的β - d - 甘露糖醛酸及其C - 5差向异构体α - l - 古洛糖醛酸以交替或随机顺序组成的片段构成。这两类分子都具有显著的生物活性（例如，细胞生长抑制活性、抗炎作用等）。在我们的研究过程中，我们结合了这两类分子的结构特征，制备了一系列含有d - 甘露糖醛酸的结构简化的硫酸乙酰肝素类似物三糖，其中还发现了α - 和β - 甘露糖苷键。由于三糖可能发挥多种生物效应且藻酸盐衍生物可影响伤口愈合过程，我们研究了合成化合物对原代人皮肤成纤维细胞的影响。我们发现，当以10 μM的浓度应用时，没有一种化合物影响细胞活力或自发胶原蛋白生成；然而，一些衍生物表现出抗炎活性并抑制了聚（I:C）诱导的白细胞介素6的释放。
