Zamani Masoud, Rodriguez Dayron M Leyva, Zhang Ziwen, Sabatini Camila, Swihart Mark T, Visser Michelle B, Cheng Chong
Department of Chemical and Biological Engineering, University at Buffalo, The State University of New York, Buffalo, NY, 14260, USA.
Department of Oral Biology, University at Buffalo, The State University of New York, Buffalo, NY, 14214, USA.
Polymer (Guildf). 2025 Jan 15;317. doi: 10.1016/j.polymer.2024.127965. Epub 2024 Dec 18.
Relative to free antibiotics, polymer-antibiotic conjugates (PACs) can possess modified solubility, sustained release behavior, and prolonged bioactivity in biological systems. As one of the most potent and ubiquitous antibiotics, clindamycin (Clin) has broad-spectrum antibiotic activity with versatile medical applications. However, polymer-Clin conjugates have not been reported yet. This can be partly ascribed to the difficulties in selective modification of Clin which possesses multiple reactive hydroxyl groups. In this study, we employed immobilized lipase as a bio-based catalyst for the facile and highly regioselective synthesis of a methacrylic-functionalized monomer-Clin conjugate via a one-step reaction. Reversible addition fragmentation chain transfer (RAFT) polymerization was then employed to synthesize copolymers of the monomer-Clin conjugate with 2-hydroxymethyl methacrylate or 3-[(3-acrylamidopropyl) dimethylammonio]propanoate to achieve water-insoluble and water-soluble Clin-containing PACs, respectively. These PACs possessed well-defined structures with high Clin content (33-46 wt%), as confirmed by H NMR and gel permeation chromatography characterizations. Living nature of the RAFT process for the synthesis of PACs was verified by a chain-extension experiment. With sustained Clin release behavior, these PACs further demonstrated notable antibacterial activities against , as verified by zone of inhibition tests. Collectively, this work presents an efficient method to synthesize different types of Clin-containing PACs, with potential for use in diverse antibacterial applications.
相对于游离抗生素，聚合物-抗生素共轭物（PACs）在生物系统中可具有改变的溶解度、缓释行为和延长的生物活性。作为最有效的和广泛存在的抗生素之一，克林霉素（Clin）具有广谱抗生素活性，有多种医学应用。然而，聚合物-克林霉素共轭物尚未见报道。这部分可归因于对具有多个反应性羟基的克林霉素进行选择性修饰存在困难。在本研究中，我们使用固定化脂肪酶作为生物基催化剂，通过一步反应简便且高度区域选择性地合成甲基丙烯酸功能化的单体-克林霉素共轭物。然后采用可逆加成-断裂链转移（RAFT）聚合反应，将单体-克林霉素共轭物与甲基丙烯酸羟甲酯或3-[(3-丙烯酰胺基丙基)二甲基铵]丙酸酯合成共聚物，分别得到水不溶性和水溶性的含克林霉素的PACs。通过1H NMR和凝胶渗透色谱表征证实，这些PACs具有明确的结构和高克林霉素含量（33-46 wt%）。通过链延伸实验验证了RAFT过程合成PACs的活性特征。这些PACs具有持续的克林霉素释放行为，通过抑菌圈试验证实，它们对[具体细菌名称未给出]还表现出显著的抗菌活性。总的来说，这项工作提出了一种高效的方法来合成不同类型的含克林霉素的PACs，具有用于多种抗菌应用的潜力。
