Identification and structural characterization of a new pro-apoptotic cyclic octapeptide cyclosaplin from somatic seedlings of Santalum album L.

Mishra, Abheepsa; Gauri, Samiran S.; Mukhopadhyay, Sourav K.; Chatterjee, S.; Das, Shibendu Sekhar; Mandal, Santi M.; Dey, Satyahari

doi:10.1016/j.peptides.2014.01.023

Cited by 30 publications

(28 citation statements)

References 60 publications

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“…In our previous work, we used the Bioinfo Meta Server to find structures similar to cyclosaplin and GROMACS, a molecular dynamics tool for predicting energy minimized structures of cyclosaplin using ab-initio procedures [9]. Briefly, a primary structure was placed up in a cubic box, including water molecules using Modeller 9.2 program [10].…”

Section: Molecular Modeling Of Cyclic Peptidementioning

confidence: 99%

“…The proteins selected for the study were Epidermal Growth Factor Receptor kinase domain previously used in our study and were used as a control in this study [9]. The files in pdb format for each receptor were converted to respective PDBQT format using MGL tools.…”

Section: Protein Preparationmentioning

confidence: 99%

“…3.7a-c. In our previous study, cyclosaplin was isolated, purified, and characterized from Santalum album L. [9]. The cyclosaplin was molecularly modeled and the energy minimized structure was further used for docking studies (Fig.…”

Section: Protein-ligand Interactionsmentioning

confidence: 99%

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Molecular Docking Studies of a Cyclic Octapeptide-Cyclosaplin from Sandalwood

Mishra¹,

Dey²

2019

Preprint

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Natural products from plants such as, chemopreventive agents attract huge attention because of their low toxicity and high specificity. The rational drug design in combination with structure based modeling and rapid screening methods offer significant potential for identifying and developing lead anticancer molecules. Thus, the molecular docking method plays an important role in screening a large set of molecules based on their free binding energies and proposes structural hypotheses of how the molecules can inhibit the target. Several peptide based therapeutics have been developed to combat several health disorders including cancers, metabolic disorders, heart-related, and infectious diseases. Despite the discovery of hundreds of such therapeutic peptides however, only few peptide-based drugs have made it to the market. Moreover, until date the activities of cyclic peptides towards molecular targets such as protein kinases, proteases, and apoptosis related proteins have never been explored. In this study we explore the in silico kinase and protease inhibitor potentials of cyclosaplin as well as study the interactions of cyclosaplin with other cancer-related proteins. Previously, the structure of cyclosaplin was elucidated by molecular modeling associated with dynamics that was used in the current study. Docking studies showed strong affinity of cyclosaplin towards cancer-related proteins. The binding affinity closer to 10 indicated efficient binding. Cyclosaplin showed strong binding affinities towards protein kinases such as EGFR, VEGFR2, PKB and p38 indicating its potential role in protein kinase inhibition. Moreover, it displayed strong binding affinity to apoptosis related proteins and revealed the possible role of cyclosaplin in apoptotic cell death. The protein-ligand interactions using LigPlot displayed some similar interactions between cyclosaplin and peptide-based ligands especially in case of protein kinases and a few apoptosis related proteins. Thus, the in silico analyses gave an insight of cyclosaplin as a potential apoptosis inducer and protein kinase inhibitor.

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Section: Molecular Modeling Of Cyclic Peptidementioning

confidence: 99%

Section: Protein Preparationmentioning

confidence: 99%

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Molecular Docking Studies of a Cyclic Octapeptide-Cyclosaplin from Sandalwood

Mishra¹,

Dey²

2019

Preprint

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“…Interference removal, analyte enrichment and high resolution separations are priorities and essentials steps preceding posterior mass spectrometry analyses and peptide characterization to access the primary amino acids sequences of peptides with unknown properties and functions [19,20].…”

Section: Peptide Prospecting In J Curcas Seedsmentioning

confidence: 99%

A new peptide from Jatropha curcas seeds: Unusual sequence and insights into its synthetic analogue that enhances proteolytic activity of papain

Jucá

Monteiro-Moreira

Moreira

et al. 2015

Process Biochemistry

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Please cite this article in press as: Jucá TL, et al. A new peptide from Jatropha curcas seeds: Unusual sequence and insights into its synthetic analogue that enhances proteolytic activity of papain. Process Biochem (2015), http://dx. a b s t r a c tA new peptide (1341 g/mol) from Jatropha curcas seeds was isolated. The linear sequence (APTLSG-GSVPRDAD) was deduced by de novo peptide sequencing, and further used as scaffold for synthesis of linear (1342 g/mol) and cyclic (1324 g/mol) synthetic analogues. The full peptide sequence was identified as inserted in a putative conserved domain of late-embryogenesis proteins which produced a significant alignment hit (100% of identity and E-value of 1e−05) with a hypothetical protein JCGZ 12502 of J. curcas. Whereas in the linear peptide predominated the double charged ion state (m/z 671.68), in the cyclic form was observed the mono charged ion state (m/z of 1325.19) and an unusual MS/MS fragmentation pattern. The differences between the forms were discrete in terms of ionic mobility, retention time (reverse phase) and net charge as function of pH. Circular dichroism spectra presented an intense negative peak at 198 nm which is assigned for its disordered contents. A negative peak at 222 nm in the spectrum of the circular form suggested its structure was not as disordered as the linear form. The peptides were neither haemolytic nor cytotoxic and did not inhibit phytopathogenic fungi. Surprisingly, the circular but not the linear peptide increased the proteolytic activity of papain.

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“…The 3D silk fibroin model was used to study the efficacy of a few anticancer drugs such as ZD6474, celexocib, and paclitaxel [19]. Our previous work identified and structurally characterized a new cyclic octapeptide cyclosaplin from somatic seedlings of Santalum album L. [20] and to further assess the efficacy of cyclosaplin we employed 3Dbased silk tumor models. There are no reports of this silk fibroin models being used to screen new peptide based anticancer agents against breast cancer.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Anticancer Efficacy of Cyclosaplin Using a Silk Based 3D Tumor Model

Mishra¹,

Mukhopadhyay²,

Dey³

2019

Preprint

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Development of novel anti-cancer peptides requires a rapid screening process which can be accelerated by using appropriate in vitro tumor models. Breast carcinoma tissue is a three dimensional (3D) microenvironment, which contains a hypoxic center surrounded by dense proliferative tissue. Biochemical clues provided by such 3D cell mass cannot be recapitulated in conventional 2D culture systems. In this experiment, we evaluate the efficacy of the sandalwood peptide, cyclosaplin on established in vitro 3D silk breast cancer model using invasive MDA-MB-231 cell line. The anti-proliferative effect of the peptide on 3D silk tumor model is monitored by alamar blue assay, with conventional 2D culture as control. The proliferation rate, glucose consumed, LDH, and MMP-9 activity of Human breast cancer cells are higher in 3D constructs compared to 2D. A higher concentration of drug is required to achieve 50% cell death in 3D culture than 2D cultures. The cyclosaplin treated MDA-MB-231 cells showed significant decrease in MMP-9 activity in 3D constructs. Microscopic analysis revealed the formation of cell clusters evenly distributed in the scaffolds. The drug treated cells were less in number, smaller and showed unusual morphology. Overall, these findings indicate the role of cyclosaplin as a promising anti-cancer therapeutics.

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Identification and structural characterization of a new pro-apoptotic cyclic octapeptide cyclosaplin from somatic seedlings of Santalum album L.

Cited by 30 publications

References 60 publications

Molecular Docking Studies of a Cyclic Octapeptide-Cyclosaplin from Sandalwood

Molecular Docking Studies of a Cyclic Octapeptide-Cyclosaplin from Sandalwood

A new peptide from Jatropha curcas seeds: Unusual sequence and insights into its synthetic analogue that enhances proteolytic activity of papain

Evaluation of Anticancer Efficacy of Cyclosaplin Using a Silk Based 3D Tumor Model

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