Wang Nan, Li Jingyang, Song Hui, Liu Chao, Hu Honggang, Liao Hongli, Cong Wei
Institute of Translational Medicine, Shanghai University Shanghai China
Department of Pediatric Respiratory Medicine, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine Shanghai China.
RSC Adv. 2020 Jul 7;10(43):25730-25735. doi: 10.1039/d0ra05136e. eCollection 2020 Jul 3.
Osteoporosis is a metabolic bone disease that is characterized by low bone mass and micro-architectural deterioration of bones. The mechanism underlying this disease implicates an imbalance between bone resorption and bone remodeling. In 2002, the US Food and Drug Administration (FDA) approved Teriparatide for the treatment of osteoporosis, and so far, this compound is the only permitted osteoanabolic. However, as a structurally flexible linear peptide, this drug may be further optimized. In this study, we develop a series of novel -acetyl glucosamine glycosylation derivatives of Teriparatide and examine their characteristics. Of the analyzed compounds, PTHG-9 exhibits enhanced helicity, greater protease stability, and increased osteoblast differentiation promoting ability compared with the original Teriparatide. Accordingly, PTHG-9 is suggested as a therapeutic candidate for postmenopausal osteoporosis (PMOP) and other related diseases. The successful development of an enhanced osteoporosis drug proves that the method proposed herein can be used to effectively enhance the chemical and biological properties of linear peptides with various biological functions.
骨质疏松症是一种代谢性骨病，其特征是骨量低和骨骼微结构恶化。这种疾病的潜在机制涉及骨吸收和骨重塑之间的失衡。2002年，美国食品药品监督管理局（FDA）批准特立帕肽用于治疗骨质疏松症，到目前为止，这种化合物是唯一被允许的骨合成代谢药物。然而，作为一种结构灵活的线性肽，这种药物可能需要进一步优化。在本研究中，我们开发了一系列特立帕肽的新型N-乙酰葡糖胺糖基化衍生物，并研究了它们的特性。在所分析的化合物中，与原始特立帕肽相比，PTHG-9表现出增强的螺旋度、更高的蛋白酶稳定性和更强的促进成骨细胞分化的能力。因此，PTHG-9被认为是绝经后骨质疏松症（PMOP）和其他相关疾病的治疗候选药物。一种增强型骨质疏松症药物的成功开发证明，本文提出的方法可用于有效增强具有各种生物学功能的线性肽的化学和生物学特性。
