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On guanidinium and cellular uptake.

Wexselblatt E, Esko JD, Tor Y - J. Org. Chem. (2014)

Bottom Line: Although impressive uptake has been demonstrated for nonoligomeric and nonpept(o)idic guanidinylated scaffolds in cell cultures and animal models, the fundamental understanding of these processes is lacking.Charge pairing and hydrogen bonding with cell surface counterparts have been proposed, but their exact role remains putative.The impact of the number and spatial relationships of the guanidinium groups on delivery and organelle/organ localization is yet to be established.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry and Biochemistry and ‡Department of Cellular and Molecular Medicine, University of California , San Diego 9500 Gilman Dr., La Jolla, California 92093, United States.

ABSTRACT
Guanidinium-rich scaffolds facilitate cellular translocation and delivery of bioactive cargos through biological barriers. Although impressive uptake has been demonstrated for nonoligomeric and nonpept(o)idic guanidinylated scaffolds in cell cultures and animal models, the fundamental understanding of these processes is lacking. Charge pairing and hydrogen bonding with cell surface counterparts have been proposed, but their exact role remains putative. The impact of the number and spatial relationships of the guanidinium groups on delivery and organelle/organ localization is yet to be established.

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Potential mechanismsfor cellular uptake including clathrin- andcaveolin-mediated endocytosis, macropinocytosis, phagocytosis, anddirect translocation across the plasma membrane.
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fig2: Potential mechanismsfor cellular uptake including clathrin- andcaveolin-mediated endocytosis, macropinocytosis, phagocytosis, anddirect translocation across the plasma membrane.

Mentions: Endocytosis, the energy-dependent vesicular uptakeof extracellularsubstrates, has been established as the main mechanism for cellularuptake of nonviral vectors.25 The mechanismsof endocytosis have been extensively reviewed by Doherty and McMahon.26 Briefly, endocytosis pathways can be dividedinto clathrin-mediated endocytosis, the best characterized endocyticpathway;27 caveolin-mediated endocytosis;28 phagocytosis, typically restricted to specializedmammalian cells;29 and macropinocytosis,which refers to the formation of large endocytic vesicles.30 They differ in the composition of the vesiclecoat (if any) and in the fate of the internalized particles.31 Although most receptors are internalized byclathrin-mediated endocytosis, other endocytic pathways are capableof selective receptor-mediated endocytosis events.32 After endocytosis, internalized cargo is trafficked intoendosomes, from where it can either escape or be sorted back to thesurface of the cell or into other compartments such as lysosomes fordegradation.33 Nonendocytic delivery wasinitially suggested for the direct translocation of cationic peptidessuch as Tat across cell membranes.34 However,the actual pathway for their entry into cells has remained controversial.35 These possible pathways for cellular uptakeare schematically depicted in Figure 2.


On guanidinium and cellular uptake.

Wexselblatt E, Esko JD, Tor Y - J. Org. Chem. (2014)

Potential mechanismsfor cellular uptake including clathrin- andcaveolin-mediated endocytosis, macropinocytosis, phagocytosis, anddirect translocation across the plasma membrane.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4120969&req=5

fig2: Potential mechanismsfor cellular uptake including clathrin- andcaveolin-mediated endocytosis, macropinocytosis, phagocytosis, anddirect translocation across the plasma membrane.
Mentions: Endocytosis, the energy-dependent vesicular uptakeof extracellularsubstrates, has been established as the main mechanism for cellularuptake of nonviral vectors.25 The mechanismsof endocytosis have been extensively reviewed by Doherty and McMahon.26 Briefly, endocytosis pathways can be dividedinto clathrin-mediated endocytosis, the best characterized endocyticpathway;27 caveolin-mediated endocytosis;28 phagocytosis, typically restricted to specializedmammalian cells;29 and macropinocytosis,which refers to the formation of large endocytic vesicles.30 They differ in the composition of the vesiclecoat (if any) and in the fate of the internalized particles.31 Although most receptors are internalized byclathrin-mediated endocytosis, other endocytic pathways are capableof selective receptor-mediated endocytosis events.32 After endocytosis, internalized cargo is trafficked intoendosomes, from where it can either escape or be sorted back to thesurface of the cell or into other compartments such as lysosomes fordegradation.33 Nonendocytic delivery wasinitially suggested for the direct translocation of cationic peptidessuch as Tat across cell membranes.34 However,the actual pathway for their entry into cells has remained controversial.35 These possible pathways for cellular uptakeare schematically depicted in Figure 2.

Bottom Line: Although impressive uptake has been demonstrated for nonoligomeric and nonpept(o)idic guanidinylated scaffolds in cell cultures and animal models, the fundamental understanding of these processes is lacking.Charge pairing and hydrogen bonding with cell surface counterparts have been proposed, but their exact role remains putative.The impact of the number and spatial relationships of the guanidinium groups on delivery and organelle/organ localization is yet to be established.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry and Biochemistry and ‡Department of Cellular and Molecular Medicine, University of California , San Diego 9500 Gilman Dr., La Jolla, California 92093, United States.

ABSTRACT
Guanidinium-rich scaffolds facilitate cellular translocation and delivery of bioactive cargos through biological barriers. Although impressive uptake has been demonstrated for nonoligomeric and nonpept(o)idic guanidinylated scaffolds in cell cultures and animal models, the fundamental understanding of these processes is lacking. Charge pairing and hydrogen bonding with cell surface counterparts have been proposed, but their exact role remains putative. The impact of the number and spatial relationships of the guanidinium groups on delivery and organelle/organ localization is yet to be established.

Show MeSH