Macromolecular Self-Assembly of Diketopiperazine Tetrapeptides

Bergeron, Raymond J.; Phanstiel, Otto; Yao, Guowei; Milstein, Sam; Weimar, William R.

doi:10.1021/ja00098a007

Cited by 46 publications

(51 citation statements)

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“…S1A). Diamine 5 was synthesized according to the method reported previously (27), which reacted with 1,2-epoxydodecane to afford cKK-E12 (Fig. 2D).…”

Section: Resultsmentioning

confidence: 99%

Lipopeptide nanoparticles for potent and selective siRNA delivery in rodents and nonhuman primates

Dong

Love

Dorkin

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

395

356

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Significance The safe, selective, and efficient delivery of siRNA is a key challenge to the broad application of siRNA therapeutics in humans. Motivated by the structure of lipoproteins, we developed lipopeptide nanomaterials for siRNA delivery. In vivo in mice, siRNA–lipopeptide particles provide the most potent delivery to hepatocytes (ED 50 ∼ 0.002 mg/kg for FVII silencing), with the highest selectivity of delivery to hepatocytes over nontarget cell types (orders of magnitude), yet reported. These materials also show efficacy in nonhuman primates.

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“…S1A). Diamine 5 was synthesized according to the method reported previously (27), which reacted with 1,2-epoxydodecane to afford cKK-E12 (Fig. 2D).…”

Section: Resultsmentioning

confidence: 99%

Lipopeptide nanoparticles for potent and selective siRNA delivery in rodents and nonhuman primates

Dong

Love

Dorkin

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

395

356

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“…7,8 These results indicate that protonation of carboxylic groups within molecular assemblies can change their structures dramatically. 9,10 Recently, a family of bolaamphiphiles was described whose protonation induced tubule and vesicle formations. 11 Our bolaamphiphiles have two carboxylic acid headgroups and the assembled structures are expected to be sensitive to solution pH.…”

mentioning

confidence: 99%

Crystalline Glycylglycine Bolaamphiphile Tubules and Their pH-Sensitive Structural Transformation

2000

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The assembled structure of the heptane bolaamphiphile, bis(N-α-amido-glycylglycine)-1,7-heptane dicarboxylate, displays a sensitivity to the acidity of a solution. At pH 4, the heptane bolaamphiphile grows to a crystalline tubule in two weeks. At pH 8, a helical ribbon structure is formed in one week. The degree of carboxylic acid protonation was used to control the final assembled structures since the structures are determined by the strengths of the amide−amide and carboxylic acid dimer hydrogen bonds. Direct structural transformation between tubules and helical ribbons was also confirmed as a function of pH using optical microscopy and Raman microscopy. Conversion from the helical ribbons to the tubules occurs within one day, while the reverse conversion, from the tubules to the helical ribbons, is ten times slower.

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“…Technosphere particles dissolve rapidly at the physiological pH of the lung and the FDKP molecules are absorbed [17][18][19][20][21][22]; hence, the dissolution of Technosphere particles was tracked by FDKP absorption (figure 3b). Maximum FDKP concentrations were observed 10 min after dosing.…”

Section: Resultsmentioning

confidence: 99%

“…Technosphere® technology is a drug delivery platform designed for the pulmonary administration of protein and peptide therapeutics [13][14][15][16][17]. It is based on the novel excipient, fumaryl diketopiperazine (FDKP; figure 1), which has the ability to self-assemble into discrete particles upon precipitation from solution [18][19][20][21][22][23]. These particles are uniform in size, optimized for inhalation into the deep lung (2-5 μm in diameter) and dissolve rapidly at physiological pH [24].…”

Section: Introductionmentioning

confidence: 99%