Synthesis and bioactivity of a Goralatide analog with antileukemic activity

Zhiliang Li; Iryna O Lebedyeva; Vita M Golubovskaya; William G Cance; Khalid A Alamry; Hassan M Faidallah; C Dennis Hall; Alan R Katritzky

doi:10.1016/j.bmc.2015.04.061

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. Epub 2015 May 14.

Authors

Zhiliang Li¹, Iryna O Lebedyeva², Vita M Golubovskaya³, William G Cance³, Khalid A Alamry⁴, Hassan M Faidallah⁴, C Dennis Hall⁵, Alan R Katritzky¹

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: charlesdennishall@gmail.com.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents / chemical synthesis*
Antineoplastic Agents / chemistry
Antineoplastic Agents / toxicity
Cell Line
Cell Proliferation / drug effects
Cell Survival / drug effects
HEK293 Cells
HL-60 Cells
Human Umbilical Vein Endothelial Cells
Humans
Oligopeptides / chemical synthesis
Oligopeptides / chemistry*
Oligopeptides / toxicity

Substances

Antineoplastic Agents
Oligopeptides
goralatide