基于改进固相多肽合成技术的前列腺靶向膜抗原的合成  

Synthesis of prostate targeted membrane antigen based on improved solid phase peptide synthesis technology

作　　者：于瀚淼 徐聪靓 曹嘉懿 徐文琪 张宸瑞 罗东 YU Hanmiao;XU Congliang;CAO Jiayi;XU Wenqi;ZHANG Chenrui;LUO Dong(Guangzhou International Campus,School of Biomedical Sciences and Engineering,South China University of Technology,Guangzhou,Guangdong 511442,China)

机构地区：[1]华南理工大学生物医学科学与工程学院广州国际校区,广东广州511442

出　　处：《中国医学工程》2025年第4期25-30,共6页China Medical Engineering

摘　　要：目的优化固相多肽合成(SPPS)技术以解决多肽链增长导致的合成效率下降、副产物增加及纯化困难等问题,提升前列腺靶向膜抗原C(Trt)Y-PSMA-1的合成效能。方法采用9-芴甲氧羰基保护基(Fmoc)化学保护策略,结合微波辅助固相合成仪与手工合成技术,以4-甲氧基苄基氨基(MBHA)树脂为固相载体,逐步构建序列为Cys-Tyr-(Lys)-Glu-Glu-Glu-Ahx-Amc-Glu'-CO-Glu(n=1,2,4)的多肽链;通过酸性条件切割多肽-树脂复合物,并利用高效液相色谱(HPLC)纯化与冷冻干燥获取终产物。结果改进方法使偶联效率提升60%,并通过手工补充合成策略解决了长链多肽合成中常见的末端环化问题。结论融合微波辅助与Fmoc保护的SPPS技术显著提高了长链多肽合成效率,为前列腺癌靶向生物材料的规模化制备提供了可重复的技术方案,相关优化策略可推广至其他功能性多肽的合成研究。【Objective】To optimize the solid-phase peptide synthesis(SPPS)technique in order to solve the problems of decreased synthesis efficiency,increased by-products,and purification difficulties caused by the growth of peptide chains,and to enhance the synthetic efficacy of prostate-targeted membrane antigen C(Trt)Y-PSMA-1.【Methods】Using Fmoc chemical protection strategy,combined with microwave-assisted solid-phase synthesizer and manual synthesis techniques,a peptide chain with sequence Cys-Tyr-(Lys)-Glu-Glu-Glu-Ahx-Amc-Glu'-CO-Glu(n=1,2,4)was constructed step by step using 4-methoxybenzylamino(MBHA)resin as a solid-phase carrier;the peptide chain was cut by acidic conditions to cleave the peptide-resin complexes,and purification and freeze-drying were utilized to obtain the final products by high performance liquid chromatography(HPLC).【Results】The improved method increased the coupling efficiency by 60%and solved the terminal cyclization problem common in the synthesis of long-chain peptides by manual complementary synthesis strategy.【Conclusion】The SPPS technology,which combines microwave-assisted and Fmoc protection,significantly improves the efficiency of long-chain peptide synthesis,and provides a reproducible technological solution for the large-scale preparation of biomaterials for prostate cancer targeting,and the related optimization strategy can be extended to the synthesis of other functional peptides.

关 键 词：固相多肽合成 9-芴甲氧羰基保护基 微波固相多肽合成仪 前列腺靶向膜抗原 

分 类 号：R977.6[医药卫生—药品] TQ464.7[医药卫生—药学]