Novel Hexapeptide Interacts with Tubulin and Microtubules, Inhibits Aβ Fibrillation, and Shows Significant Neuroprotection

Biswas, Atanu; Kurkute, Prashant; Saleem, Suraiya; Jana, Batakrishna; Mohapatra, Saswat; Mondal, Prasenjit; Adak, Anindyasundar; Ghosh, Subhajit; Saha, Abhijit; Bhunia, Debmalya; Biswas, Subhash Chandra; Ghosh, Surajit

doi:10.1021/acschemneuro.5b00149

Cited by 27 publications

(41 citation statements)

References 29 publications

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“…The characteristic peak at 1641 cm −1 wavelength (Figure S7, Supporting Information) corresponds to the parallel β‐sheet structure. In fact, peptides with such β‐sheet like conformation are known to form vesicle like morphology . Thus, we checked the morphology of TTP assembly using transmission electron microscopic (TEM) imaging and Cryo‐EM (cryo‐electron microscopy).…”

Section: Resultsmentioning

confidence: 99%

“…In fact, any peptide‐based nanoassembly for the delivery of DX toward its target site was not studied before. Herein, we report tubulin specific delivery of DX using a tubulin targeted dodecapeptide (TTP), designed from α, β ‐tubulin heterodimer interface, which can spontaneously self‐assemble to form nanovesicle and entraps docetaxel drug ( Scheme ). This combination showed synergistic action of peptide and DX as they can bind at different sites of tubulin.…”

Section: Introductionmentioning

confidence: 99%

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Synergistic Anticancer Effect of Peptide‐Docetaxel Nanoassembly Targeted to Tubulin: Toward Development of Dual Warhead Containing Nanomedicine

Mohapatra

Saha

Mondal

et al. 2016

Adv Healthcare Materials

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Microtubule dynamics play a crucial role in cancer cell division. Various drugs are developed to target microtubule. Although a few of them show potential in treatment of cancer, but success rate is limited due to their poor bioavailability and lack of specificity. Thus, development of highly bioavailable and target specific anticancer drug is extremely necessary. To address these key issues, here, a combination of approaches such as development of a dodecapeptide-docetaxel nanoassembly targeted to tubulin and MUC1 (mucin 1, cell surface associated glycoprotein) targeting oligonucleotide aptamer conjugated liposome for delivering peptide-docetaxel nanoassembly into the breast cancer cell have been demonstrated. These studies reveal that the peptide forms nanoassembly and entraps docetaxel drug. Further, the liposomal formulation of peptide-docetaxel exerts synergistic anticancer effect, activates key mitotic check point proteins, and inhibits bipolar spindle formation, metastatic cancer cell migration, and growth of tumor mimicking 3D multicellular spheroid.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Synergistic Anticancer Effect of Peptide‐Docetaxel Nanoassembly Targeted to Tubulin: Toward Development of Dual Warhead Containing Nanomedicine

Mohapatra

Saha

Mondal

et al. 2016

Adv Healthcare Materials

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“…Interestingly, microtubules have long been known as a key factor for AZD and are recently emerging as potential targets for thrombotic disease . Regardless, available candidates for enhancing microtubule assembly are mostly chemotherapeutic agents or nonphysiological synthetic peptides . Their application tends to be hampered by potential cytotoxicity and immunoneutralization.…”

Section: Discussionmentioning

confidence: 99%

Humanin analogue, HNG, inhibits platelet activation and thrombus formation by stabilizing platelet microtubules

Ren

You

et al. 2020

J Cellular Molecular Medi

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HNG, a highly potent mutant of the anti‐Alzheimer peptide‐humanin, has been shown to protect against ischaemia‐reperfusion (I/R) injury. However, the underlying mechanism related to platelet activation remains unknown. We proposed that HNG has an effect on platelet function and thrombus formation. In this study, platelet aggregation, granule secretion, clot retraction, integrin activation and adhesion under flow conditions were evaluated. In mice receiving HNG or saline, cremaster arterial thrombus formation induced by laser injury, tail bleeding time and blood loss were recorded. Platelet microtubule depolymerization was evaluated using immunofluorescence staining. Results showed that HNG inhibited platelet aggregation, P‐selectin expression, ATP release, and αIIbβ3 activation and adhesion under flow conditions. Mice receiving HNG had attenuated cremaster arterial thrombus formation, although the bleeding time was not prolonged. Moreover, HNG significantly inhibited microtubule depolymerization, enhanced tubulin acetylation in platelets stimulated by fibrinogen or microtubule depolymerization reagent, nocodazole, and inhibited AKT and ERK phosphorylation downstream of HDAC6 by collagen stimulation. Therefore, our results identified a novel role of HNG in platelet function and thrombus formation potentially through stabilizing platelet microtubules via tubulin acetylation. These findings suggest a potential benefit of HNG in the management of cardiovascular diseases.

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“…After that glass slides were thoroughly washed with water and dried under stream of nitrogen gas. Surface functionalization was done by performing following stepwise methods . GOPTS was treated at 75 °C for 90 min for the silanisation of glass surfaces.…”

Section: Methodsmentioning

confidence: 99%

“…Surface functionalization was done by performing following stepwise methods. [47] GOPTS was treated at 75 8Cf or 90 min for the silanisation of glass surfaces. Next, silanised glass surfaces were treated with diamino-polyethylene glycol and heated at 75 8Cf or overnight.…”

Section: Methodsmentioning

confidence: 99%

Probing Deviation of Adhered Membrane Dynamics between Reconstituted Liposome and Cellular System

Mondal

Chowdhury

Nandi

et al. 2019

Chemistry An Asian Journal

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The dynamics of cell-cell adhesion are complicated due to complexities in cellular interactions and intra-membrane interactions. In the present work, we have reconstituted al iposome-based model system to mimic the cell-cell adhesion process. Our model liposome system consists of one fluorescein-taggeda nd one TRITC (tetramethyl-rhodamine isothiocyanate)-tagged liposome, adhered through biotinneutravidin interaction. We monitored the adhesion process in liposomes using Fçrster Resonance EnergyT ransfer (FRET) between fluorescein( donor) and TRITC (acceptor). Occurrence of FRET is confirmed by the decrease in donor lifetime as well as distinct rise time of the acceptorf luorescence. Interestingly,t he acceptor'se mission exhibits fluctuations in the range of % 3 AE 1s.T his may be attributed to structural oscillationsa ssociated in two adhered liposomesa rising from the flexible nature of biotin-neutravidin interaction. We have compared the dynamics in ac ell-mimicking liposome system with that in an in vitro live cell system.I nt he adhered live cell system, we used CPM (7-diethylamino-3-(4maleimido-phenyl)-4-methylcoumarin, donor) andn ile red (acceptor), whicha re known to stain the membrane of CHO (Chinese Hamster Ovary) cells. The dynamicso ft he adhered membranes of two live CHO cells were observed through FRET between CPM and nile red. The acceptorf luorescence intensity exhibits an oscillation in the time-scaleo f% 1 AE 0.75 s, which is faster comparedt ot he reconstituted liposome system,i ndicating the contributions and involvement of multiple dynamic protein complexes around the cell membrane. This study offers simple reconstituted model systems to understand the complex membrane dynamics using aF RET-based physical chemistry approach.[a] Dr.

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Novel Hexapeptide Interacts with Tubulin and Microtubules, Inhibits Aβ Fibrillation, and Shows Significant Neuroprotection

Cited by 27 publications

References 29 publications

Synergistic Anticancer Effect of Peptide‐Docetaxel Nanoassembly Targeted to Tubulin: Toward Development of Dual Warhead Containing Nanomedicine

Synergistic Anticancer Effect of Peptide‐Docetaxel Nanoassembly Targeted to Tubulin: Toward Development of Dual Warhead Containing Nanomedicine

Humanin analogue, HNG, inhibits platelet activation and thrombus formation by stabilizing platelet microtubules

Probing Deviation of Adhered Membrane Dynamics between Reconstituted Liposome and Cellular System

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