Yang Xiantao, Li Linji, Li Rong, Li Xiang, Li Shuna, Su Chunli, Liao Hongli
School of Pharmacy, Chengdu Medical College, 783 Xindu Avenue, Xindu District, Chengdu 610500, China.
Pidu area center, Chengdu Institute of Food Inspection, 456 Yong'an West Rd., Ande Street, Pidu District, Chengdu 611730, China.
Org Biomol Chem. 2025 May 7;23(18):4471-4479. doi: 10.1039/d5ob00398a.
Melittin is a natural antimicrobial peptide isolated from bee venom, and the non-specific cytotoxicity and hemolytic activity severely limit its clinical application. Glycosylation of proteins is very common in physiological and biochemical processes and can modulate the interaction of proteins with their target. In this study, eight glycosyl groups were used to modify the arginine of melittin at sites 22 and/or 24, and single and double arginine -glycosylated peptides were designed and synthesized. Among the acquired 24 glycopeptides, MLT-1c, MLT-3c, MLT-1f, MLT-3f, MLT-1g, and MLT-3h were found to possess higher helicity, while MLT-3c, MLT-3f and MLT-3h showed dramatically reduced hemolytic activity, especially MLT-3c, whose HC value is 199.3 μM. MLT-1a, MLT-3a and MLT-2c exhibited improved inhibitory activity against , and the MIC was 4 μg mL. MLT-1e and MLT-2g have the strongest tolerance to trypsase, and MLT-3c has the highest therapeutic index. In general, rhamnosyl-modified melittin MLT-3c could be a potent agent for antibacterial and antitumor therapy with high stability and low hemolytic side effects.
蜂毒肽是一种从蜂毒中分离出的天然抗菌肽，其非特异性细胞毒性和溶血活性严重限制了它的临床应用。蛋白质糖基化在生理和生化过程中非常普遍，并且可以调节蛋白质与其靶标的相互作用。在本研究中，使用八个糖基修饰蜂毒肽22位和/或24位的精氨酸，设计并合成了单精氨酸糖基化和双精氨酸糖基化的肽段。在所获得的24种糖肽中，发现MLT-1c、MLT-3c、MLT-1f、MLT-3f、MLT-1g和MLT-3h具有更高的螺旋度，而MLT-3c、MLT-3f和MLT-3h的溶血活性显著降低，尤其是MLT-3c，其溶血浓度值为199.3 μM。MLT-1a、MLT-3a和MLT-2c对[具体对象未给出]的抑制活性有所提高，最小抑菌浓度为4 μg/mL。MLT-1e和MLT-2g对胰蛋白酶的耐受性最强，MLT-3c具有最高的治疗指数。总体而言，鼠李糖基化修饰的蜂毒肽MLT-3c可能是一种用于抗菌和抗肿瘤治疗的有效药物，具有高稳定性和低溶血副作用。
