Arginine-rich cyclic peptides enhance cellular delivery of anticancer agents: Molecular insights

Antara Banerjee, Naser Sayeh, Amir Nasrolahi Shirazi, Rakesh Tiwari, Keykavous Parang, Arpita Yadav

Research output: Contribution to journalArticlepeer-review

Abstract

Research in the area of cancer treatment has undergone a paradigm shift from design of new anticancer agents to efficient drug delivery systems trying to overcome cytotoxicity aspects and bioavailability problems. We have reported earlier two cyclic peptides [WR]4 and [WG(triazole-KRNH2)]3 for the delivery of phosphopeptides and have considered them for the purpose of enhancing delivery of anticancer drugs. This study attempts to understand at the molecular level self-assembly of cyclic peptides containing tryptophan and arginine residues and their suitability as molecular transporters of anti-HIV and anticancer agents. Ab initio molecular orbital calculations coupled with molecular dynamics simulation studies are reported along with flow cytometry results to show self-assemblage of these cyclic peptides induced by counterions. Our results show the suitability of [WR]4 system in enhancing the delivery of lamivudine and dasatinib in conformity with experimental results. The conformational flexibility, charge environment and HLB of these peptides play an important role in determining their drug delivery capabilities. To our knowledge, this is the first attempt to explain the self-assembly and molecular transporter properties of these systems at the molecular level.

Original languageEnglish (US)
Pages (from-to)591-604
Number of pages14
JournalLetters in Drug Design and Discovery
Volume13
Issue number7
StatePublished - Aug 1 2016
Externally publishedYes

Keywords

  • Ab initio
  • Arginine-rich cyclic peptides
  • Dasatinib
  • Molecular dynamics simulations
  • Molecular orbital calculations
  • Molecular transporter
  • Self assemblage
  • Tryptophan containing

ASJC Scopus subject areas

  • Pharmaceutical Science
  • Drug Discovery
  • Molecular Medicine

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