Simerska Pavla, Abdel-Aal Abu-Baker M, Fujita Yoshio, Moyle Peter M, McGeary Ross P, Batzloff Michael R, Olive Colleen, Good Michael F, Toth Istvan
School of Molecular and Microbial Sciences , The University of Queensland, St Lucia 4072, Queensland, Australia.
J Med Chem. 2008 Mar 13;51(5):1447-52. doi: 10.1021/jm701410p. Epub 2008 Feb 16.
Group A streptococcus (GAS) is associated with many human diseases, ranging in severity from benign to life-threatening. A promising strategy for developing vaccines against GAS involves the use of carbohydrates as carriers for peptide antigens. This study describes the optimized synthesis of d-glucose and d-galactose derived carriers, bearing an adipate linker and four tert-butoxycarbonyl protected aminopropyl groups. Prophylactic GAS vaccine candidates were synthesized by conjugating multiple copies of a single GAS M protein derived peptide antigen (either J8 or J14) onto the carbohydrate carriers. These antigens contain peptide sequences, which are highly conserved and offer the potential to prevent infections caused by up to 70% of GAS strains. Lipophilic amino acids were also conjugated to the d-glucose anomeric carbon to produce a self-adjuvanting liposaccharide vaccine. High serum IgG antibody titers against each of the incorporated peptide epitopes were detected following subcutaneous immunization of B10.BR (H-2 (k)) mice with the liposaccharide vaccine candidates.
A组链球菌(GAS)与许多人类疾病相关,严重程度从良性到危及生命不等。开发针对GAS疫苗的一种有前景的策略涉及使用碳水化合物作为肽抗原的载体。本研究描述了具有己二酸酯连接基和四个叔丁氧羰基保护的氨丙基的d - 葡萄糖和d - 半乳糖衍生载体的优化合成。通过将单个GAS M蛋白衍生肽抗原(J8或J14)的多个拷贝缀合到碳水化合物载体上,合成了预防性GAS疫苗候选物。这些抗原包含高度保守的肽序列,有可能预防高达70%的GAS菌株引起的感染。还将亲脂性氨基酸缀合到d - 葡萄糖异头碳上,以制备自佐剂脂糖疫苗。在用脂糖疫苗候选物皮下免疫B10.BR(H - 2(k))小鼠后,检测到针对每个掺入的肽表位的高血清IgG抗体滴度。