Amphiphilic bicyclic peptides as cellular delivery agents

Donghoon Oh; Shaban Anwar Darwish; Amir Nasrolahi Shirazi; Rakesh Kumar Tiwari; Keykavous Parang

doi:10.1002/cmdc.201402230

Amphiphilic bicyclic peptides as cellular delivery agents

Donghoon Oh, Shaban Anwar Darwish, Amir Nasrolahi Shirazi, Rakesh Kumar Tiwari, Keykavous Parang

Research output: Contribution to journal › Article

Abstract

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.

Original language	English (US)
Pages (from-to)	2449-2453
Number of pages	5
Journal	ChemMedChem
Volume	9
Issue number	11
DOIs	https://doi.org/10.1002/cmdc.201402230
State	Published - Nov 1 2014
Externally published	Yes

Keywords

amphiphiles
bicyclic peptides
cell-penetrating
drug delivery
endocytosis

ASJC Scopus subject areas

Pharmacology, Toxicology and Pharmaceutics(all)
Organic Chemistry
Molecular Medicine
Medicine(all)

Access to Document

10.1002/cmdc.201402230

Fingerprint Dive into the research topics of 'Amphiphilic bicyclic peptides as cellular delivery agents'. Together they form a unique fingerprint.

Cite this

Oh, D., Darwish, S. A., Shirazi, A. N., Tiwari, R. K., & Parang, K. (2014). Amphiphilic bicyclic peptides as cellular delivery agents. ChemMedChem, 9(11), 2449-2453. https://doi.org/10.1002/cmdc.201402230

@article{44d1ee5d807e4ef58ea388f4efdae542,

title = "Amphiphilic bicyclic peptides as cellular delivery agents",

abstract = "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.",

keywords = "amphiphiles, bicyclic peptides, cell-penetrating, drug delivery, endocytosis",

author = "Donghoon Oh and Darwish, {Shaban Anwar} and Shirazi, {Amir Nasrolahi} and Tiwari, {Rakesh Kumar} and Keykavous Parang",

year = "2014",

month = nov,

day = "1",

doi = "10.1002/cmdc.201402230",

language = "English (US)",

volume = "9",

pages = "2449--2453",

journal = "ChemMedChem",

issn = "1860-7179",

publisher = "John Wiley and Sons Ltd",

number = "11",

}

TY - JOUR

T1 - Amphiphilic bicyclic peptides as cellular delivery agents

AU - Oh, Donghoon

AU - Darwish, Shaban Anwar

AU - Shirazi, Amir Nasrolahi

AU - Tiwari, Rakesh Kumar

AU - Parang, Keykavous

PY - 2014/11/1

Y1 - 2014/11/1

N2 - 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.

AB - 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.

KW - amphiphiles

KW - bicyclic peptides

KW - cell-penetrating

KW - drug delivery

KW - endocytosis

UR - http://www.scopus.com/inward/record.url?scp=84928983926&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84928983926&partnerID=8YFLogxK

U2 - 10.1002/cmdc.201402230

DO - 10.1002/cmdc.201402230

M3 - Article

C2 - 25047914

AN - SCOPUS:84928983926

VL - 9

SP - 2449

EP - 2453

JO - ChemMedChem

JF - ChemMedChem

SN - 1860-7179

IS - 11

ER -