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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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Crystalstructures and 2D representations of (a) free base guanidine,16 (b) a guanidinium carboxylate salt,20 (c) a propylguanidinium phosphate salt,21 and (d) a sulfate salt of a synthetic bisguanidiniumreceptor.22
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fig1: Crystalstructures and 2D representations of (a) free base guanidine,16 (b) a guanidinium carboxylate salt,20 (c) a propylguanidinium phosphate salt,21 and (d) a sulfate salt of a synthetic bisguanidiniumreceptor.22

Mentions: Guanidine, first isolated in 1861 by oxidizingguanine,13 is found in a wide variety ofnatural products,including the amino acid arginine.14 Althoughknown for more than 150 years, the first solid-state structure wassolved in 2007 by co-crystallization with 2-amino-4,6-dimethyl-1,3,5-triazine.15 Two years later, the structure of the free basewas reported,16 and more recently, neutrondiffraction studies accurately positioned the hydrogen atoms (Figure 1a).17 As a strong base(pKb ≈ 0.5), at physiological pH’sguanidine exists in its protonated form, the highly stabilized guanidiniumcation.


On guanidinium and cellular uptake.

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

Crystalstructures and 2D representations of (a) free base guanidine,16 (b) a guanidinium carboxylate salt,20 (c) a propylguanidinium phosphate salt,21 and (d) a sulfate salt of a synthetic bisguanidiniumreceptor.22
© Copyright Policy
Related In: Results  -  Collection

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

fig1: Crystalstructures and 2D representations of (a) free base guanidine,16 (b) a guanidinium carboxylate salt,20 (c) a propylguanidinium phosphate salt,21 and (d) a sulfate salt of a synthetic bisguanidiniumreceptor.22
Mentions: Guanidine, first isolated in 1861 by oxidizingguanine,13 is found in a wide variety ofnatural products,including the amino acid arginine.14 Althoughknown for more than 150 years, the first solid-state structure wassolved in 2007 by co-crystallization with 2-amino-4,6-dimethyl-1,3,5-triazine.15 Two years later, the structure of the free basewas reported,16 and more recently, neutrondiffraction studies accurately positioned the hydrogen atoms (Figure 1a).17 As a strong base(pKb ≈ 0.5), at physiological pH’sguanidine exists in its protonated form, the highly stabilized guanidiniumcation.

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