Cysteine and arginine-rich peptides as molecular carriers

Amir Nasrolahi Shirazi, Naglaa Salem El-Sayed, Dindayal Mandal, Rakesh K. Tiwari, Kathy Tavakoli, Matthew Etesham, Keykavous Parang

Research output: Contribution to journalArticle

Abstract

A number of linear and cyclic peptides containing alternative arginine and cysteine residues, namely linear (CR)3, linear (CR)4, linear (CR)5, cyclic [CR]4, and cyclic [CR]5, were synthesized. The peptides were evaluated for their ability to deliver two molecular cargos, fluorescence-labeled cell-impermeable negatively charged phosphopeptide (F′-GpYEEI) and fluorescence-labeled lamivudine (F′-3TC), intracellularly in human leukemia cancer (CCRF-CEM) cells. We investigated the role of cyclization and the number of amino acids in improving the transporting ability of the peptides. The flow cytometry studies suggested that the synthesized peptides were able to work efficiently as transporters for both cargos. Among all compounds, cyclic [CR]4 was found to be the most efficient peptide in transporting the cargo into cells. For instance, the cellular uptake of F′-3TC (5 μM) and F′-GpYEEI (5 μM) was enhanced by 16- and 20-fold, respectively, in the presence of cyclic [CR]4 compared to that of the parent compound alone. The mechanism of F′-GpYEEI uptake by cells was found to be energy-independent. The results showed that the number of amino acids and their cyclic nature can impact the efficiency of the peptide in transporting the molecular cargos.

Original languageEnglish (US)
Pages (from-to)656-661
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Volume26
Issue number2
DOIs
StatePublished - Jan 15 2016
Externally publishedYes

Fingerprint

Cysteine
Arginine
Lamivudine
Peptides
Cyclic Amino Acids
Fluorescence
Phosphopeptides
Cyclic Peptides
Flow cytometry
Cyclization
Flow Cytometry
Leukemia
Amino Acids
Neoplasms

Keywords

  • Arginine
  • Cysteine
  • Drug delivery
  • Formulation
  • Peptide

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Molecular Biology
  • Molecular Medicine
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

Cite this

Shirazi, A. N., El-Sayed, N. S., Mandal, D., Tiwari, R. K., Tavakoli, K., Etesham, M., & Parang, K. (2016). Cysteine and arginine-rich peptides as molecular carriers. Bioorganic and Medicinal Chemistry Letters, 26(2), 656-661. https://doi.org/10.1016/j.bmcl.2015.11.052

Cysteine and arginine-rich peptides as molecular carriers. / Shirazi, Amir Nasrolahi; El-Sayed, Naglaa Salem; Mandal, Dindayal; Tiwari, Rakesh K.; Tavakoli, Kathy; Etesham, Matthew; Parang, Keykavous.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 26, No. 2, 15.01.2016, p. 656-661.

Research output: Contribution to journalArticle

Shirazi, AN, El-Sayed, NS, Mandal, D, Tiwari, RK, Tavakoli, K, Etesham, M & Parang, K 2016, 'Cysteine and arginine-rich peptides as molecular carriers', Bioorganic and Medicinal Chemistry Letters, vol. 26, no. 2, pp. 656-661. https://doi.org/10.1016/j.bmcl.2015.11.052
Shirazi AN, El-Sayed NS, Mandal D, Tiwari RK, Tavakoli K, Etesham M et al. Cysteine and arginine-rich peptides as molecular carriers. Bioorganic and Medicinal Chemistry Letters. 2016 Jan 15;26(2):656-661. https://doi.org/10.1016/j.bmcl.2015.11.052
Shirazi, Amir Nasrolahi ; El-Sayed, Naglaa Salem ; Mandal, Dindayal ; Tiwari, Rakesh K. ; Tavakoli, Kathy ; Etesham, Matthew ; Parang, Keykavous. / Cysteine and arginine-rich peptides as molecular carriers. In: Bioorganic and Medicinal Chemistry Letters. 2016 ; Vol. 26, No. 2. pp. 656-661.
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