糖二蛋白:一种合成的糖蛋白模仿酶,具有分支糖显示,强烈抑制细菌聚合
Phillip M Rendle1, Andreas Seger, Joao Rodrigues
1Department of Chemistry, University of Oxford, Mansfield Road, Oxford OX1 3TA, UK.
Journal of the American Chemical Society
|April 15, 2004
概括
新的合成葡萄糖蛋白模仿剂有效地阻断了致病性细菌的附着. 这些大分子配体比小分子抑制剂有效抑制细菌聚合超过一百万倍,提供了一种新的抗感染策略.
科学领域:
- 微生物学 微生物学
- 生物化学 生物化学
- 药物发现 药物发现 药物发现
背景情况:
- 抗生素耐药性需要新的抗感染策略.
- 通过粘合素介导的细菌附着对感染和毒性至关重要.
- 用小分子模仿复杂的天然合体来形成粘合素是具有挑战性的.
研究的目的:
- 为了开发合成的葡萄糖蛋白模仿,准细菌粘合素.
- 创建强大的细菌附着和聚合的抑制剂.
主要方法:
- 利用蛋白质降解酶作为合成模仿物的支架.
- 设计的大分子蛋白质连接体来结合细菌粘附素.
- 评估模仿剂在抑制细菌聚合方面的有效性.
主要成果:
- 开发了精确的合成葡萄糖蛋白模仿剂,能够结合粘合素.
- 在显著高水平上实现了致病性细菌聚合的抑制.
- 与小分子抑制剂相比,其疗效超过百万倍.
结论:
- 合成葡萄糖蛋白模仿剂代表了对抗细菌感染的有希望的治疗方法.
- 开发出来的连接体提供了一种强有力的策略,可以阻断细菌粘合素并预防感染.
- 这种方法为传统抗生素提供了可行的替代方案,用于对抗细菌病原性.
相关概念视频
Protein and Protein Structure
Proteins are one of the most abundant organic molecules in living systems and have the most diverse range of functions of all macromolecules. Proteins may be structural, regulatory, contractile, or protective. They may serve in transport, storage, or membranes; or they may be toxins or enzymes. Their structures, like their functions, vary greatly. They are all, however, amino acid polymers arranged in a linear sequence.
A protein's shape is critical to its function. For example, an enzyme can...
A protein's shape is critical to its function. For example, an enzyme can...
Single-Strand DNA Binding Proteins
For successful DNA replication, the unwinding of double-stranded DNA must be accompanied by stabilization and protection of the separated single strands of the DNA. This crucial task is performed by single-strand DNA-binding (SSB) proteins. They bind to the DNA in a sequence-independent manner, which means that the nitrogenous bases of the DNA need not be present in a specific order for binding of SSB proteins to it. The binding of SSB proteins straightens single-stranded DNA (ssDNA) and makes...
Insulin: Biosynthesis, Chemistry, and Preparation
The endoplasmic reticulum (ER) of pancreatic β-cells synthesizes preproinsulin, which consists of a signal peptide, A and B chains, and a C-peptide. Preproinsulin is then cleaved and folded into proinsulin, which translocates to the Golgi apparatus for sorting and packaging into secretory granules. In these granules, enzymatic clipping generates insulin and C-peptide.
Damage or functional impairment of β-cells inhibits insulin production, leading to diabetes. Diabetes treatment primarily uses...
Damage or functional impairment of β-cells inhibits insulin production, leading to diabetes. Diabetes treatment primarily uses...
Peptidoglycan Synthesis
Structure of PeptidoglycanPeptidoglycan is a vital structural component of the bacterial cell wall, providing mechanical strength and shape to the cell. It consists of repeating units of two sugars—N-acetylglucosamine (NAG) and N-acetylmuramic acid (NAM)—linked by β-1,4 glycosidic bonds. These sugar chains are cross-linked by short peptide chains, forming a mesh-like polymer that surrounds the bacterial plasma membrane.Cytoplasmic Phase – Precursor SynthesisPeptidoglycan biosynthesis begins in...
Production of Pharmaceuticals
Industrial insulin production uses genetically engineered E. coli expressing a proinsulin gene controlled by a tryptophan promoter and containing a methionine linker for later cleavage. The cells also carry ampicillin resistance for selective growth. Seed cultures are stored at −80 °C and production begins by thawing a small amount to inoculate starter cultures, which are progressively scaled to a 50,000-L bioreactor. In the bioreactor, E. coli grow in nutrient-rich media under sterile, tightly...
Inhibitors of Gram-positive Cell Wall Synthesis
Bacterial cell walls are typically rigid structures composed mainly of peptidoglycan, a mesh-like polymer that provides mechanical strength and maintains cell shape. The synthesis of peptidoglycan is a crucial process in bacterial growth and serves as a primary target for many antibiotics.Mechanism of Action of Beta-Lactam AntibioticsBeta-lactam antibiotics, such as penicillin, inhibit peptidoglycan synthesis in actively growing cells. These antibiotics share a characteristic four-membered...


