6205-69-2Relevant articles and documents
Synthesis and anti-osteoporosis activity of novel Teriparatide glycosylation derivatives
Cong, Wei,Hu, Honggang,Li, Jingyang,Liao, Hongli,Liu, Chao,Song, Hui,Wang, Nan
, p. 25730 - 25735 (2020)
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 N-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.
Radical-Mediated Acyl Thiol-Ene Reaction for Rapid Synthesis of Biomolecular Thioester Derivatives
Lynch, Dylan M.,McLean, Joshua T.,McSweeney, Lauren,Milbeo, Pierre,Scanlan, Eoin M.
supporting information, p. 4148 - 4160 (2021/08/24)
The thiol-ene ‘click’ reaction has emerged as a versatile process for carbon–sulfur bond formation with widespread applications in chemical biology, medicinal chemistry and materials science. Thioesters are key intermediates in a wide range of synthetic and biological processes and efficient methods for their synthesis are of considerable interest. Herein, we report the first examples of acyl-thiol-ene (ATE) for the synthesis of biomolecular thioesters, including peptide, lipid and carbohydrate derivatives. A key finding is the profound effect of the amino acid side chain on the outcome of the ATE reaction. Furthermore, radical generated thioesters underwent efficient S-to-N acyl transfer and desulfurisation to furnish ‘sulfur-free’ ligation products in an overall amidation process with diverse applications for chemical ligation and bioconjugation.
Total Synthesis of Glycosylated Human Interferon-γ
Ashhurst, Anneliese S.,Dowman, Luke J.,Fairbanks, Antony J.,Kwan, Ann,Larance, Mark,Li, Henry Y.,Payne, Richard J.,Wang, Xiaoyi,Watson, Emma E.
supporting information, p. 6863 - 6867 (2020/09/15)
Interferon-γ(IFN-γ) is a glycoprotein that is responsible for orchestrating numerous critical immune induction and modulation processes and is used clinically for the treatment of a number of diseases. Herein, we describe the total chemical synthesis of homogeneously glycosylated variants of human IFN-γusing a tandem diselenide-selenoester ligation-deselenization strategy in the C- to N-terminal direction. The synthetic glycoproteins were successfully folded, and the structures and antiviral functions were assessed.
