Sarkar Biswajit, Mahapa Avisek, Dey Kalyan, Manhas Rakshit, Chatterji Dipankar, Jayaraman Narayanaswamy
Department of Organic Chemistry, Indian Institute of Science Bangalore 560 012 India
Molecular Biophysics Unit, Indian Institute of Science Bangalore 560 012 India
RSC Adv. 2023 Feb 3;13(7):4669-4677. doi: 10.1039/d2ra08196b. eCollection 2023 Jan 31.
The benign nature of aza-Michael addition reaction in aqueous solutions is demonstrated herein to conduct a direct glycoconjugation of amine-terminated poly(ether imine) (PETIM) dendrimers. Zero to three generations of dendrimers, possessing up to 16 amine functionalities at their peripheries, undergo aza-Michael reaction with unsaturated sugar vinyl sulfoxide in aq. MeOH solutions and afford the corresponding dendrimers modified with multiple glycosyl moieties at the periphery. First order kinetics of the glycoconjugation is monitored at varying temperatures and the rate constants are observed to be 60-508 s, for zero and first generation dendrimers. The antibacterial effects of amine-terminated dendrimers and the corresponding glycoconjugates are studied across Gram-positive, Gram-negative and acid-fast bacteria. Among the species, and showed the greatest growth inhibition effect at micromolar concentrations, for the native amine-terminated and the corresponding glycoconjugated dendrimers. Quantitative assays are performed to adjudge the inhibition efficacies of dendrimers and the glycoconjugates. Selectivity to inhibit and growth, and minimal effects on other bacterial species by dendrimers and glycoconjugates are emphasized.
本文展示了水溶液中氮杂-Michael加成反应的良性本质，以进行胺基封端的聚（醚亚胺）（PETIM）树枝状大分子的直接糖缀合。零至三代树枝状大分子在其外围具有多达16个胺官能团，在甲醇水溶液中与不饱和糖乙烯基亚砜发生氮杂-Michael反应，并在外围提供用多个糖基部分修饰的相应树枝状大分子。在不同温度下监测糖缀合的一级动力学，观察到零代和第一代树枝状大分子的速率常数为60-508 s⁻¹。研究了胺基封端的树枝状大分子和相应糖缀合物对革兰氏阳性菌、革兰氏阴性菌和抗酸菌的抗菌作用。在这些物种中，对于天然胺基封端的和相应的糖缀合树枝状大分子，[具体物种1]和[具体物种2]在微摩尔浓度下显示出最大的生长抑制作用。进行定量分析以判断树枝状大分子和糖缀合物的抑制效果。强调了树枝状大分子和糖缀合物对[具体物种1]和[具体物种2]生长的选择性抑制以及对其他细菌物种的最小影响。
