The synthesis, distribution, and anti-hepatic cancer activity of YSL

• Published in: Bioorganic & medicinal chemistry Vol. 12; no. 18; pp. 4989 - 4994
• Main Authors: Ding, Wenfeng, Zhang, Jiali, Yao, Zhi, Lu, Rong, Wu, Dezhu, Li, Ginfu, Shen, Zilong, Sun, Yingji, Lin, Gang, Wang, Chao, Zhao, Ming, Peng, Shiqi
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 15.09.2004; Elsevier Science
• Subjects: [3,5-3H-Tyr]-Ser-Leu-OH; Animals; Anti-hepatic cancer; Antineoplastic agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - metabolism; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Contrast media. Radiopharmaceuticals; Distribution; General aspects; Humans; Liver Neoplasms - drug therapy; Liver Neoplasms - metabolism; Macaca mulatta; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Nude; Oligopeptides - chemical synthesis; Oligopeptides - metabolism; Oligopeptides - therapeutic use; Pharmacology. Drug treatments; Rats; Xenograft Model Antitumor Assays - statistics & numerical data; YSL; Anti-hepatic cancer; [3,5-3H-Tyr]-Ser-Leu-OH; YSL; Distribution; Intraperitoneal administration; Intravenous administration; Radiolabelling; Peptides; Liver; Rodentia; Tripeptide; Tritium; Hydrogen Isotopes; Malignant tumor; Tissue; Vertebrata; Chemotherapy; Mammalia; Treatment; Mouse; Animal; Digestive diseases; Peptide synthesis; Pharmacokinetics; Chemical synthesis
• DOI: 10.1016/j.bmc.2004.06.030
• ISSN: 0968-0896

(I) HCl/CH3OH; (II) DCC/HOBt/NMM with corresponding carboxyl component; (III) HCl/CH3CO2C2H5 (6mol/L); (IV) NaOH/H2O/CH3OH; (V) 3H2 and 10% Pd/C. YSL was prepared stepwise from C terminal to N terminal with the side chain un-protective amino acids, Boc-Leu-OMe, Boc-Ser-OH, and Boc-Tyr-OH, as the starting materials in 39.5% total yield (31.2g/per batch). With the side chain un-protective Boc-(3,5-dibromo)-Tyr-OH and HCl·Ser-Leu-OMe as the starting materials (3,5-3H-Tyr)-Ser-Leu-OH was obtained in 29% yield. The determination of radioactive quantity in the urine and feces indicated that even after the administration for 130h only 8.4% (5.35% in urine and 3.05% in feces) of total radioactive quantity from the metabolite of [3,5-3H-Tyr]-Ser-Leu-OH were monitored. The distribution study revealed the relative accumulation level of the individual tissue was arranged in the sequence of spleen>liver>kidney>lung>heart>muscle>brain. Selecting hepatic cancer as the target YSL significantly increased the survival time of H22 tumor cells implanted mice.