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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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Bicyclic chiral guanidinium tetramer.74
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fig14: Bicyclic chiral guanidinium tetramer.74

Mentions: A family of tetraguanidinium vectors that efficiently internalizedin human tumor cells was reported by Giralt and co-workers.74 These vectors consist of chiral bicyclic guanidiniumsubunits linked together through short thioether spacers (Figure 14). It was shown that these compounds translocatedthrough HeLa membranes more efficiently than Antp or Tat peptidesat very low concentrations.74 These compoundsappear to specifically accumulate in mitochondria and showed no cytotoxicityat relevant concentrations. Following kinetic and temperature-dependentexperiments showed that the internalization pathway involved bothactive energy-dependent transport and passive internalization.74


On guanidinium and cellular uptake.

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

Bicyclic chiral guanidinium tetramer.74
© Copyright Policy
Related In: Results  -  Collection

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

fig14: Bicyclic chiral guanidinium tetramer.74
Mentions: A family of tetraguanidinium vectors that efficiently internalizedin human tumor cells was reported by Giralt and co-workers.74 These vectors consist of chiral bicyclic guanidiniumsubunits linked together through short thioether spacers (Figure 14). It was shown that these compounds translocatedthrough HeLa membranes more efficiently than Antp or Tat peptidesat very low concentrations.74 These compoundsappear to specifically accumulate in mitochondria and showed no cytotoxicityat relevant concentrations. Following kinetic and temperature-dependentexperiments showed that the internalization pathway involved bothactive energy-dependent transport and passive internalization.74

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