Self-assembled dipeptide nanotubes constituted by flexible β-phenylalanine and conformationally constrained α,β-dehydrophenylalanine residues as drug delivery system

Parween, Shaheena; Misra, Abha; Ramakumar, Suryanarayanarao; Chauhan, Virander S.

doi:10.1039/c3tb21856b

Cited by 40 publications

(26 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Though the finding of peptide NTs in a cell environment is difficult, it can be achieved by proper imaging methods. Similar TEM studies have been reported recently in different contexts [4,20,21]. Even though the sample preparation is laborious, it gives direct imaging of peptide NTs in cells.…”

Section: Nanotubes Uptake In Cho Cellssupporting

confidence: 81%

“…5(a and b)) which is promising for use of NTs in drug delivery as well as in imaging study. Moreover, dipeptides showed no cytotoxicity toward HeLa and L929 cells, and were able to encapsulate small drug molecules; further showed that anticancerous drug mitoxantrone was more efficient in killing HeLa and B6F10 cells when entrapped in nanotubes as compared to free mitoxantrone, biocompatible and proteolytically stable drug delivery vehicles [4]. Many of the functionalization techniques that have been reported for in vivo imaging in the literature [22] suffer from drawbacks such as difficult synthesis steps, poor biocompatibility and low stability.…”

Section: Nanotubes Uptake In Cho Cellsmentioning

confidence: 99%

“…Interest in studying this peptide based self-assembly by scientists from different scientific fields has grown tremendously due to their potential large scale applications in biomedical sciences [3]. These nanostructures are stable on heating up to 150 • C and at an extensive range of pH [4]. The reported mechanism of the formation of NTs is due to H-bonding, aromatic interaction like -stacking [5], and a zipper [6] like interaction between the aromatic rings.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Simple size-selective separation and microscopic characterization of Phe–Phe nanotubes and study of its internalization inside CHO cells

Karthikeyan

Giri

Kulkarni

et al. 2014

J Microsc Ultrastruct

View full text Add to dashboard Cite

a b s t r a c tPhe-Phe nanotube internalization in Chinese hamster ovary (CHO) cells is imaged through the transmission electron microscopic (TEM) study. Size-selective separation of peptide nanotubes (NTs) is of great value when we think about its application in biocompatible drug delivery. This paper describes a simple size-selective separation protocol for separating Phe-Phe NTs. During the synthesis, it is commonly observed that peptide NTs are formed with a range of sizes in their width and length and hence easy separation techniques of NTs are essential. Removal of the monomers from NTs is also important. Microscopic imaging of peptide NTs is also important in this context and particularly when these are used in the diagnostic and therapeutic purposes. Herein, we report a straightforward size-selective separation of peptide NTs by size exclusion chromatography (SEC) and imaging the fractions through TEM, confocal, and deconvolution microscopic techniques. Here, we report, for the first time, use of deconvolution fluorescence microscopy to detect NTs. As commonly used photo microscope cannot resolve the images of very small particles (e.g., less than micron scale), electron microscopy is widely used in imaging of NPs. Hence, systematic peptide NTs separation followed by these characterization techniques provides an option to study the internalization of NTs inside cells. Intake of peptide NTs inside cells is promising for their use in drug delivery as well as in imaging study.

show abstract

Section: Nanotubes Uptake In Cho Cellssupporting

confidence: 81%

Section: Nanotubes Uptake In Cho Cellsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Simple size-selective separation and microscopic characterization of Phe–Phe nanotubes and study of its internalization inside CHO cells

Karthikeyan

Giri

Kulkarni

et al. 2014

J Microsc Ultrastruct

View full text Add to dashboard Cite

show abstract

“…β‐PA is an important aromatic β‐amino acid that is also part of the antitumor agent paclitaxel and the antitumor antibiotic C‐1027 . Besides this, β‐PA and derivatives thereof can also be utilized in β‐peptides, as inhibitor for peptidase IV and in drug‐delivery systems . The β‐PA‐converting ω‐TA from S. thermophiles shows only a low activity of 3.3 U mg −1 compared to the ω‐TA from Variovorax paradoxus with a specific activity of 17.5 U mg −1 at 37 °C .…”

Section: Introductionmentioning

confidence: 97%

Improvement in the Thermostability of a β‐Amino Acid Converting ω‐Transaminase by Using FoldX

et al. 2017

View full text Add to dashboard Cite

ω-Transaminases (ω-TAs) are important biocatalysts for the synthesis of active, chiral pharmaceutical ingredients containing amino groups, such as β-amino acids, which are important in peptidomimetics and as building blocks for drugs. However, the application of ω-TAs is limited by the availability and stability of enzymes with high conversion rates. One strategy for the synthesis and optical resolution of β-phenylalanine and other important aromatic β-amino acids is biotransformation by utilizing an ω-transaminase from Variovorax paradoxus. We designed variants of this ω-TA to gain higher process stability on the basis of predictions calculated by using the FoldX software. We herein report the first thermostabilization of a nonthermostable S-selective ω-TA by FoldX-guided site-directed mutagenesis. The melting point (T ) of our best-performing mutant was increased to 59.3 °C, an increase of 4.0 °C relative to the T value of the wild-type enzyme, whereas the mutant fully retained its specific activity.

show abstract

“…Dehydroamino acids continuously attract attention in various areas, mainly in synthesis, as designed products or suitable substrates, including asymmetric hydrogenation as well as in the conformational studies . Dehydrophenylalanine (ΔPhe), although scarcely presented in natural compounds, is the most often studied dehydroamino acid . This is mainly due to its relatively high stability as well as promising works on dehydrophenylalanyl analogs of naturally occurred peptides .…”

Section: Introductionmentioning

confidence: 99%

Conformational preferences and synthesis of isomers Z and E of oxazole‐dehydrophenylalanine

et al. 2016

View full text Add to dashboard Cite

Dehydrophenylalanine, ΔPhe, is the most commonly studied α,β-dehydroamino acid. In nature, further modifications of the α,β-dehydroamino acids were found, for example, replacement of the C-terminal amide group by oxazole ring. The conformational properties of oxazole-dehydrophenylalanine residue (ΔPhe-Ozl), both isomers Z and E, were investigated. To determine all possible conformations, theoretical calculations were performed using Ac-(Z/E)-ΔPhe-Ozl(4-Me) model compounds at M06-2X/6-31++G(d,p) level of theory. Ac-(Z/E)-ΔPhe-Ozl-4-COOEt compounds were synthesized and the conformational preferences of each isomer, Z and E, were investigated using FTIR and NMR-NOE in solutions of increasing polarity (CHCl3 , DMSO-d6). The solid-state low-temperature structures of Ac-(Z)-ΔPhe-Ozl-4-COOEt and its intermediate analog Ac-(Z)-ΔPhe-Ozn(4-OH)-4-COOEt were also determined. In a weakly polar environment, the ΔPhe-Ozl residue has a tendency to adopt the conformation β2 with the calculated φ and ψ angles of -127° and 0° for the isomer Z and -170° and 26° for the isomer E. The increase of environment polarity favors the helical conformation α and the beta-turn like conformation β, but the conformation β2 seems to be still accessible. The (E)-ΔPhe-Ozl residue can be obtained from the isomer Z in photoisomerization reaction. However, hydroxyl-oxazoline-dehydrophenylalanine ΔPhe-Ozn(4-OH) decomposes in such conditions. Alternatively, (E)-ΔPhe-NH2 can be applied as a substrate in the Hantzsch reaction. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 106: 283-294, 2016.

show abstract

Self-assembled dipeptide nanotubes constituted by flexible β-phenylalanine and conformationally constrained α,β-dehydrophenylalanine residues as drug delivery system

Cited by 40 publications

References 46 publications

Simple size-selective separation and microscopic characterization of Phe–Phe nanotubes and study of its internalization inside CHO cells

Simple size-selective separation and microscopic characterization of Phe–Phe nanotubes and study of its internalization inside CHO cells

Improvement in the Thermostability of a β‐Amino Acid Converting ω‐Transaminase by Using FoldX

Conformational preferences and synthesis of isomers Z and E of oxazole‐dehydrophenylalanine

Contact Info

Product

Resources

About