Synthesis and bioactivity of a Goralatide analog with antileukemic activity

  • Bioorg Med Chem. 2015 Aug 1;23(15):5056-5060. doi: 10.1016/j.bmc.2015.04.061.
Zhiliang Li  1 ,  Iryna O Lebedyeva  2 ,  Vita M Golubovskaya  3 ,  William G Cance  3 ,  Khalid A Alamry  4 ,  Hassan M Faidallah  4 ,  C Dennis Hall  5 ,  Alan R Katritzky  1
Affiliations
  • 1. Center for Heterocyclic Compounds, Department of Chemistry, University of Florida, Gainesville, FL 32611-7200, United States.
  • 2. Center for Heterocyclic Compounds, Department of Chemistry, University of Florida, Gainesville, FL 32611-7200, United States; Department of Chemistry and Physics, Georgia Regents University, 1120 15th Street SCI W3005, Augusta, GA 30912, United States.
  • 3. Department of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, NY 14263, United States.
  • 4. Chemistry Department, Faculty of Science, King Abdulaziz University, Jeddah 21589, Saudi Arabia.
  • 5. Center for Heterocyclic Compounds, Department of Chemistry, University of Florida, Gainesville, FL 32611-7200, United States. Electronic address: [email protected].
PMID: 26048023 DOI: 10.1016/j.bmc.2015.04.061
Abstract

Natural tetrapeptide Goralatide (AcSDKP) is a selective inhibitor of primitive haematopoietic cell proliferation. It is not stable in vivo and decomposes within 4.5min when applied to live cells. In this work we developed an analog of Goralatide that exhibits cytotoxicity towards human myeloid HL-60, HEL, Nalm-6 leukemia cells, endothelial HUVEC, glioblastoma U251 and transformed kidney 293T cells. The Goralatide analog showed significant stability in organic solution with no tendency to degrade oxidatively.

Keywords
Anticancer; Antileukemic; Goralatide; Peptide; Peptidomimetic.
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