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

Bioorg Med Chem. 2004 Sep 15;12(18):4989-94. doi: 10.1016/j.bmc.2004.06.030.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / therapeutic use*
  • Humans
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / metabolism
  • Macaca mulatta
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Oligopeptides / chemical synthesis*
  • Oligopeptides / metabolism
  • Oligopeptides / therapeutic use*
  • Rats
  • Xenograft Model Antitumor Assays / statistics & numerical data

Substances

  • Antineoplastic Agents
  • Oligopeptides
  • H-Tyr-Ser-Leu-OH