Comparative Molecular Transporter Properties of Cyclic Peptides Containing Tryptophan and Arginine Residues Formed through Disulfide Cyclization
| Autor: | Dindyal Mandal, Rakesh Tiwari, Magdy A. H. Zahran, Keykavous Parang, Eman H M Mohammed, Amany Mostafa Osman, Saghar Mozaffari |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Arginine
phosphopeptide Stereochemistry Cell Survival Pharmaceutical Science Cell-Penetrating Peptides 01 natural sciences Article Analytical Chemistry lcsh:QD241-441 03 medical and health sciences chemistry.chemical_compound Drug Delivery Systems lcsh:Organic chemistry Cell Line Tumor Drug Discovery Peptide synthesis Humans cancer Disulfides Physical and Theoretical Chemistry Cytotoxicity 030304 developmental biology Cell Proliferation chemistry.chemical_classification 0303 health sciences Molecular Structure 010405 organic chemistry Phosphopeptide Organic Chemistry disulfide bridge Tryptophan cellular uptake Transporter Cyclic peptide 0104 chemical sciences chemistry Chemistry (miscellaneous) Cyclization drug delivery Cell-penetrating peptide Molecular Medicine cytotoxicity cell-penetrating peptide |
| Zdroj: | Molecules, Vol 25, Iss 2581, p 2581 (2020) Molecules Volume 25 Issue 11 |
| ISSN: | 1420-3049 |
| Popis: | We have previously reported cyclic cell-penetrating peptides [WR]5 and [WR]4 as molecular transporters. To optimize further the utility of our developed peptides for targeted therapy in cancer cells using the redox condition, we designed a new generation of peptides and evaluated their cytotoxicity as well as uptake behavior against different cancer cell lines. Thus, cyclic [C(WR)xC] and linear counterparts (C(WR)xC), where x = 4&ndash 5, were synthesized using Fmoc/tBu solid-phase peptide synthesis, purified, and characterized. The compounds did not show any significant cytotoxicity (at 25 µ M) against ovarian (SK-OV-3), leukemia (CCRF-CEM), gastric adenocarcinoma (CRL-1739), breast carcinoma (MDA-MB-231), and normal kidney (LLCPK) cells after 24 and 72 h incubation. Both cyclic [C(WR)5C] and linear (C(WR)5C) demonstrated comparable molecular transporter properties versus [WR]5 in the delivery of a phosphopeptide (F&prime GpYEEI) in CCRF-CEM cells. The uptake of F&prime GpYEEI in the presence of 1,4-dithiothreitol (DTT) as the reducing agent was significantly improved in case of l(C(WR)5C), while it was not changed by [C(WR)5C]. Fluorescence microscopy also demonstrated a significant uptake of F&prime GpYEEI in the presence of l(C(WR)5C). Cyclic [C(WR)5C] improved the uptake of the fluorescent-labeled anti-HIV drugs F&prime d4T, F&prime 3TC, and F&prime FTC by 3.0&ndash 4.9-fold. These data indicate that both [C(WR)5C] and linear (C(WR)5C) peptides can act as molecular transporters. |
| Databáze: | OpenAIRE |
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