Amphiphilic Bicyclic Peptides as Cellular Delivery Agents. Issue 11 (22nd July 2014)

• Record Type: Journal Article
• Authors: Oh, Donghoon; Darwish, Shaban Anwar; Shirazi, Amir Nasrolahi; Tiwari, Rakesh Kumar; Parang, Keykavous
• Is Part Of: ChemMedChem. Volume 9:Issue 11(2014:Nov.)
• Page Start: 2449
• Page End: 2453
• Publication Date: 2014-07-22
• Subjects: Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.201402230
• Languages: English
• ISSNs: 1860-7179

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>Two bicyclic peptides composed of tryptophan and arginine residues were synthesized from monocyclic peptide building blocks and evaluated as cellular delivery agents. [W₅G]‐(triazole)‐[KR₅] and [W₅E]‐(β‐Ala)‐[KR₅] containing triazole and β‐alanine linkers improved the cellular delivery of fluorescein (F′)‐labeled phosphopeptide F′‐GpYEEI (F′‐PP) by 7.6‐ and 19.3‐fold, respectively, in human ovarian adenocarcinoma cells. However, parent monocyclic peptide [R₅] and monocyclic peptide [WR]₄ only enhanced the cellular uptake of the phosphopeptide by only 1.3‐ and 3.7‐fold, respectively. Confocal microscopy showed that the corresponding fluorescein‐labeled bicyclic peptide F′‐[KW₄E]‐(β‐Ala)‐[KR₅] was localized in the cytosol and nucleus. Studying the cellular uptake of F′‐[KW₄E]‐(β‐Ala)‐[KR₅] in the presence of endocytosis inhibitors indicated that the clathrin‐ and caveolin‐dependent endocytosis are the main pathways for cellular uptake. The bicyclic peptide was able to improve antiproliferative activity of doxorubicin by 20 %. These data suggest that this bicyclic peptide can be utilized as a new class of cell‐penetrating peptides and cellular delivery tools.</p> </abstract>