Synthesis and Evaluation of Tripodal Peptide Analogues for Cellular Delivery of Phosphopeptides

Ye, Guofeng; Nam, Nguyen Hai; Kumar, Anil; Saleh, A.A.M.; Shenoy, Dinesh B.; Amiji, Mansoor M.; Lin, Xiaofeng; Sun, Gongqin; Parang, Keykavous

doi:10.1021/jm070416o

Cited by 37 publications

(30 citation statements)

References 45 publications

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“…HTB-19) cells by 10-fold. 30 A comparative FACS study exhibited that the cellular uptake of F′-PEpYLGLD (10 µM) enhanced approximately 6 times in the presence of LP4 (50 µM) in CCRF-CEM cells after 1 h incubation. Thus, the transporting efficiency of LPA4 for F′-PEpYLGLD was significantly less than that of the cyclic [WR] 4 that showed 24-fold higher cellular delivery of the same phosphopeptide after 1 h incubation (Figure 3).…”

Section: Resultsmentioning

confidence: 99%

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Efficient Delivery of Cell Impermeable Phosphopeptides by a Cyclic Peptide Amphiphile Containing Tryptophan and Arginine

Shirazi

Tiwari

et al. 2013

Mol. Pharmaceutics

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Phosphopeptides are valuable reagent probes for studying protein-protein and protein-ligand interactions. The cellular delivery of phosphopeptides is challenging because of the presence of the negatively charged phosphate group. The cellular uptake of a number of fluorescent-labeled phosphopeptides, including F′-GpYLPQTV, F′-NEpYTARQ, F′-AEEEIYGEFEAKKKK, F′-PEpYLGLD, F′-pYVNVQN-NH2, and F′-GpYEEI (F′ = fluorescein) was evaluated in the presence or absence of a [WR]4, a cyclic peptide containing alternative arginine (R) and tryptophan (W) residues, in human leukemia cells (CCRF-CEM) after 2 h incubation using flow cytometry. [WR]4 improved significantly the cellular uptake of all phosphopeptides. PEpYLGLD is a sequence that mimics the pTyr1246 of ErbB2 that is responsible for binding to the Chk SH2 domain. The cellular uptake of F′-PEpYLGLD was enhanced dramatically by 27-fold in the presence of [WR]4 and was found to be time-dependent. Confocal microscopy of a mixture of F′-PEpYLGLD and [WR]4 in live cells exhibited intracellular localization and significantly higher cellular uptake compared to that of F′-PEpYLGLD alone. Transmission Electron Microscopy (TEM) and Isothermal Calorimetric (ITC) were used to study the interaction of PEpYLGLD and [WR]4. TEM results showed that the mixture of PEpYLGLD and [WR]4 formed noncircular nanosized structures with width and height of 125 and 60 nm, respectively. ITC binding studies confirmed the interaction between [WR]4 and PEpYLGLD. The binding isotherm curves, derived from sequential binding models, showed an exothermic interaction driven by entropy. These studies suggest that amphiphilic peptide [WR]4 can be used as a cellular delivery tool of cell-impermeable negatively charged phosphopeptides.

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Section: Resultsmentioning

confidence: 99%

“…30 The linear positively charged peptides were designed based on the Src SH2 domain phosphotyrosine (pTyr) binding pocket.…”

Section: Introductionmentioning

confidence: 99%

Efficient Delivery of Cell Impermeable Phosphopeptides by a Cyclic Peptide Amphiphile Containing Tryptophan and Arginine

Shirazi

Tiwari

et al. 2013

Mol. Pharmaceutics

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“…Then 20 μl of 2nd stock were added to each well of the 96‐well plates (final 0.1% DMSO). The plates were further incubated for 48 h. Cytotoxicity of the compounds was measured by the colorimetric method, as described previously with slight modifications . The IC 50 values were calculated using a Probits method .…”

Section: Methodsmentioning

confidence: 99%

“…The plates were further incubated for 48 h. Cytotoxicity of the compounds was measured by the colorimetric method, as described previously [36] with slight modifications. [37] [38] The IC 50 values were calculated using a Probits method. [38] Data represent means AE standard errors of the mean (SEM) of at least three independent experiments, each performed in triplicate.…”

Section: Cytotoxicity Assaymentioning

confidence: 99%

Quinazoline‐Based Hydroxamic Acids: Design, Synthesis, and Evaluation of Histone Deacetylase Inhibitory Effects and Cytotoxicity

Hieu

Anh

Pham-The

et al. 2018

Chemistry & Biodiversity

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In our search for novel histone deacetylases inhibitors, we have designed and synthesized a series of novel hydroxamic acids and N-hydroxybenzamides incorporating quinazoline heterocycles (4a - 4i, 6a - 6i). Bioevaluation showed that these quinazoline-based hydroxamic acids and N-hydroxybenzamides were potently cytotoxic against three human cancer cell lines (SW620, colon; PC-3, prostate; NCI-H23, lung). In term of cytotoxicity, several compounds, e.g., 4g, 4c, 4g - 4i, 6c, and 6h, displayed from 5- up to 10-fold higher potency than SAHA (suberoylanilidehydroxamic acid, vorinostat). The compounds were also generally comparable to SAHA in inhibiting HDACs with IC values in sub-micromolar range. Some compounds, e.g., 4g, 6c, 6e, and 6h, were even more potent HDAC inhibitors compared to SAHA in HeLa extract assay. Docking studies demonstrated that the compounds tightly bound to HDAC2 at the active binding site with binding affinities higher than that of SAHA. Detailed investigation on the estimation of absorption, distribution, metabolism, excretion, and toxicity (ADMET) suggested that compounds 4g, 6c, and 6g, while showing potent HDAC2 inhibitory activity and cytotoxicity, also potentially displayed ADMET characteristics desirable to be expected as promising anticancer drug candidates.

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“…Acidic macromolecules are therefore considered to play a key role in biomineralization processes [15][16][17]. Nevertheless, there are other characteristics of proteins which play important roles in biomineralization such as the total net charge of the chain, hydrophobicity and hydrogen bonding capacity [18]. To date however, despite many years of research, little information is available about the structure-activity relationships in the proteins that control the formation of calcium carbonate in nature.…”

Section: Introductionmentioning

confidence: 99%

Random Poly(Amino Acid)s Synthesized by Ring Opening Polymerization as Additives in the Biomimetic Mineralization of CaCO3

Dmitrović

Habraken²,

Hendrix

et al. 2012

Polymers

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Biominerals such as bones, teeth and seashells, very often have advanced material properties and are a source of inspiration for material chemists. As in biological systems acidic proteins play an important role in regulating the formation of CaCO 3 biominerals, we employ poly(amino acid)s to mimic the processes involved in the laboratory. Here we report on the synthesis of random aminoacid copolymers of glutamic acid (Glu), lysine (Lys) and alanine (Ala) using the ring opening polymerization (ROP) of their respective N-carboxy anhydrides (NCA). The synthetic approach yields a series of polymers with different monomer composition but with similar degrees of polymerization (DP 45-56) and comparable polydispersities (PDI 1.2-1.6). Using random copolymers we can investigate the influence of composition on the activity of the polymers without having OPEN ACCESSPolymers 2012, 4 1196 to take into account the effects of secondary structure or specific sequences. We show that variation of the Glu content of the polymer chains affects the nucleation and thereby also the particle size. Moreover, it is shown that the polymers with the highest Glu content affect the kinetics of mineral formation such that the first precipitate is more soluble than in the case of the control.

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Synthesis and Evaluation of Tripodal Peptide Analogues for Cellular Delivery of Phosphopeptides

Cited by 37 publications

References 45 publications

Efficient Delivery of Cell Impermeable Phosphopeptides by a Cyclic Peptide Amphiphile Containing Tryptophan and Arginine

Efficient Delivery of Cell Impermeable Phosphopeptides by a Cyclic Peptide Amphiphile Containing Tryptophan and Arginine

Quinazoline‐Based Hydroxamic Acids: Design, Synthesis, and Evaluation of Histone Deacetylase Inhibitory Effects and Cytotoxicity

Random Poly(Amino Acid)s Synthesized by Ring Opening Polymerization as Additives in the Biomimetic Mineralization of CaCO3

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