Synthesis, characterization and anti-cancer activity of a peptide nucleolipid bioconjugate

Niki Rana; Suiying Huang; Pradeepkumar Patel; Uri Samuni; David Sabatino

doi:10.1016/j.bmcl.2016.06.020

Synthesis, characterization and anti-cancer activity of a peptide nucleolipid bioconjugate

Bioorg Med Chem Lett. 2016 Aug 1;26(15):3567-71. doi: 10.1016/j.bmcl.2016.06.020. Epub 2016 Jun 9.

Authors

Niki Rana¹, Suiying Huang², Pradeepkumar Patel¹, Uri Samuni², David Sabatino³

Affiliations

¹ Department of Chemistry and Biochemistry, Seton Hall University, 400 South Orange Avenue, South Orange, NJ 07079, United States.
² Department of Chemistry, Queens College, City University of New York, 65-30 Kissena Blvd, Flushing, New York 11367, United States; The Ph.D. Programs in Chemistry and Biochemistry, The Graduate Center of the City University of New York, New York, NY 10016, United States.
³ Department of Chemistry and Biochemistry, Seton Hall University, 400 South Orange Avenue, South Orange, NJ 07079, United States. Electronic address: david.sabatino@shu.edu.

PMID: 27329798
DOI: 10.1016/j.bmcl.2016.06.020

Abstract

The synthesis, characterization and anti-cancer activity of a novel peptide nucleolipid bioconjugate is reported in this study. The prerequisite 5'-carboxy derived nucleolipid was synthesized following a five-step solution-phase approach and then coupled to the cytotoxic D-(KLAKLAK)2 sequence by solid-phase bioconjugation. The biophysical and structural properties of the peptide-nucleolipid bioconjugate were evaluated and compared to the peptide controls. These characterization studies revealed that the amphiphilic peptides favored helical-type secondary structures and well-defined nanoparticle formulations that were found to be contributive towards their biological activity. The peptide-nucleolipid bioconjugate displayed greater lethality in comparison to the native D-(KLAKLAK)2AK sequence when treated within the human A549 non-small cell lung carcinoma cell line. Thus, the amphiphilic peptide-nucleolipid forms a new class of anti-cancer peptides that may be developed into promising leads in the fight against cancer.

Keywords: Amphiphilic peptides; Anti-cancer activity; Nucleolipid; Peptide bioconjugate.

Publication types

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

MeSH terms

Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Cell Death / drug effects
Cell Line, Tumor
Cell Proliferation / drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Humans
Lipids / chemistry
Lipids / pharmacology*
Molecular Structure
Peptides / chemistry
Peptides / pharmacology*
Structure-Activity Relationship

Substances

Antineoplastic Agents
Lipids
Peptides