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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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Dendrimer-like transporters: (a) dendronized nanoparticles,67 (b) “vivo morpholinos”,68 and (c) a representative structure of guanidiniumcarbon nanotubes.69
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fig12: Dendrimer-like transporters: (a) dendronized nanoparticles,67 (b) “vivo morpholinos”,68 and (c) a representative structure of guanidiniumcarbon nanotubes.69

Mentions: As mentioned above, the use of high-order guanidinylateddendrimerswas reviewed by Gillies et al.40 Relatedreports, include different platforms such as dendronized nanoparticles,67 “vivo-morpholinos”,68 and guanidinium dendron–carbon nanotubes(Figure 12).69 Jeongand co-workers encapsulated a hydrophobic peptide model drug intodendritic amine and guanidinium group-modified nanoparticles.67 In this system, up to four amine or guanidiniumgroups are connected to a hydrophobic stearyl tail through a shortoligophenylalanine linker introduced to provide structural rigidity(Figure 12a).67 Itwas shown that the uptake efficiency increased with the number ofthe positively charged groups and that guanidinium-functionalizednanoparticles had better ability to cross membranes than the amino-functionalizedones. Moreover, no significant cytotoxicity was observed for the tetravalentcarriers.67


On guanidinium and cellular uptake.

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

Dendrimer-like transporters: (a) dendronized nanoparticles,67 (b) “vivo morpholinos”,68 and (c) a representative structure of guanidiniumcarbon nanotubes.69
© Copyright Policy
Related In: Results  -  Collection

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

fig12: Dendrimer-like transporters: (a) dendronized nanoparticles,67 (b) “vivo morpholinos”,68 and (c) a representative structure of guanidiniumcarbon nanotubes.69
Mentions: As mentioned above, the use of high-order guanidinylateddendrimerswas reviewed by Gillies et al.40 Relatedreports, include different platforms such as dendronized nanoparticles,67 “vivo-morpholinos”,68 and guanidinium dendron–carbon nanotubes(Figure 12).69 Jeongand co-workers encapsulated a hydrophobic peptide model drug intodendritic amine and guanidinium group-modified nanoparticles.67 In this system, up to four amine or guanidiniumgroups are connected to a hydrophobic stearyl tail through a shortoligophenylalanine linker introduced to provide structural rigidity(Figure 12a).67 Itwas shown that the uptake efficiency increased with the number ofthe positively charged groups and that guanidinium-functionalizednanoparticles had better ability to cross membranes than the amino-functionalizedones. Moreover, no significant cytotoxicity was observed for the tetravalentcarriers.67

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