Department of Chemical Sciences and Technologies, University of Rome "Tor Vergata", via della Ricerca Scientifica 1, 00133 Rome, Italy.
School of Pharmacy, East Anglia University, Norwich NR4 7TJ, UK.
Molecules. 2017 Oct 27;22(11):1843. doi: 10.3390/molecules22111843.
Thymosin α1 (Tα1), is a peptidic hormone, whose immune regulatory properties have been demonstrated both in vitro and in vivo and approved in different countries for treatment of several viral infections and cancers. Tα1 assumes a conformation in negative membranes upon insertion into the phosphatidylserine exposure as found in several pathologies and in apoptosis. These findings are in agreement with the pleiotropy of Tα1, which targets both normal and tumor cells, interacting with multiple cellular components, and have generated renewed interest in the topic. Hyaluronan (HA) occurs ubiquitously in the extracellular matrix and on cell surfaces and has been related to a variety of diseases, and developmental and physiological processes. Proteins binding HA, among them CD44 and the Receptor for HA-mediated motility (RHAMM) receptors, mediate its biological effects. NMR spectroscopy indicated preliminarily that an interaction of Tα1 with HA occurs specifically around lysine residues of the sequence LKEKK of Tα1 and is suggestive of a possible interference of Tα1 in the binding of HA with CD44 and RHAMM. Further studies are needed to deepen these observations because Tα1 is known to potentiate the T-cell immunity and anti-tumor effect. The binding inhibitory activity of Tα1 on HA-CD44 or HA-RHAMM interactions can suppress both T-cell reactivity and tumor progression.
胸腺肽 α1（Tα1）是一种肽类激素，其免疫调节特性已在体外和体内得到证实，并在不同国家获得批准，用于治疗多种病毒感染和癌症。Tα1 在插入暴露的磷脂酰丝氨酸时，在负膜中呈现出一种构象，这种构象在多种病理和细胞凋亡中都有发现。这些发现与 Tα1 的多功能性一致，Tα1 靶向正常细胞和肿瘤细胞，与多种细胞成分相互作用，这一主题重新引起了人们的兴趣。透明质酸（HA）普遍存在于细胞外基质和细胞表面，与多种疾病以及发育和生理过程有关。与 HA 结合的蛋白质，包括 CD44 和透明质酸介导运动受体（RHAMM）受体，介导其生物学效应。NMR 光谱学初步表明，Tα1 与 HA 之间的相互作用特异性地发生在 Tα1 的序列 LKEKK 的赖氨酸残基周围，这表明 Tα1 可能干扰 HA 与 CD44 和 RHAMM 的结合。需要进一步研究来深化这些观察结果，因为 Tα1 已知可增强 T 细胞免疫和抗肿瘤作用。Tα1 对 HA-CD44 或 HA-RHAMM 相互作用的结合抑制活性可以抑制 T 细胞反应性和肿瘤进展。
