抗HIV融合多肽CP32M的制备工艺研究

摘要

Objective: In order to provide a large quantity of CP32M, an anti-HIV-1 fusion peptide, for its pre-clinical trial, we probe its large scale of synthesis. Methods: CP32M was synthesized by using combined solid-liquid method, the crude peptide was purified by DEAE anion exchange chromatography and RP-HPLC. Results: Three optimized fragments which were easily synthesized and coupled were found, CP32M with purity more than 98% was obtained after the purification of DEAE anion exchange chromatography and RP-HPLC. Conclusion: The arrangement of three fragments (Ac-1-9-OH, Fmoc-10-21-OH, H-22-32-NH2) of CP32M could significantly elevate the yield of fragment syntheses and couplings, and DEAE anion exchange chromatography could efficiently isolate the impurities and increase the yield of the RP-HPLC purification in the second step.%目的:研究抗HIV融合多肽CP32M的制备工艺,为其临床前试验奠定基础.方法:采用固-液相混合策略规模合成目标肽,用离子交换色谱、反相高效液相色谱对粗肽进行纯化.结果:获得了利于提高合成及片段缩合效率的3条优选片段,CP32M粗品经DEAE离子交换色谱及C18反相纯化后纯度高于98％.结论:CP32M按3条片段(Ac-1-9-OH 、Fmoc- 10-21-OH 、H-22-32-NH2)划分,可显著提高片段合成及缩合效率,DEAE阴离子交换色谱能除去大部分杂质,提高了第二步C18反相色谱纯化效率.