The synthesis, distribution, and anti-hepatic cancer activity of YSL.
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-(3)H-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 130 h only 8.4% (5.35% in urine and 3.05% in feces) of total radioactive quantity from the metabolite of [3,5-(3)H-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.
Ding
Wenfeng
W
College of Pharmaceutical Sciences, Peking University, Beijing 100083, PR China.
Zhang
Jiali
J
Yao
Zhi
Z
Lu
Rong
R
Wu
Dezhu
D
Li
Ginfu
G
Shen
Zilong
Z
Sun
Yingji
Y
Lin
Gang
G
Wang
Chao
C
Zhao
Ming
M
Peng
Shiqi
S
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000378:metabolism / Q000627:therapeutic use*; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D008253:Macaca mulatta; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000378:metabolism / Q000627:therapeutic use*; D051381:Rats; D023041:Xenograft Model Antitumor Assays / Q000706:statistics & numerical data
D000970:Antineoplastic Agents; D009842:Oligopeptides; C484773:H-Tyr-Ser-Leu-OH