PXD017924

PXD017924 is an original dataset announced via ProteomeXchange.

Title	Discovery and mechanistic studies of cytotoxic cyclotides from the medicinal herb Hybanthus enneaspermus (Linn) F. Muell
Description	Cyclotides are a family of plant-derived peptides characterized by a ~30 amino acid cyclic backbone and a cystine knot motif. Cyclotides have diverse bioactivities, and in particular their cytotoxicity has attracted significant attention for its potential anti-cancer applications. Hybanthus enneaspermus is a medicinal herb widely used in India as a natural libido enhancer, and a previous study indicated that it may contain cyclotides. In the current study, 11 novel cyclotides and one known cyclotide (cycloviolacin O2) were identified and isolated from H. enneaspermus. Their sequences were determined using tandem MS, and NMR analysis of six of these cyclotides indicates their three-dimensional structures are similar to those of other known cyclotides. The most abundant cyclotide in this plant, hyen D, has comparable cytotoxicity against cancer cells to cycloviolacin O2, the most cytotoxic cyclotide discovered so far. Herein we provide a mechanistic insight into the mode-of-action of the novel cyclotides’ cytotoxicity. Hyen D, E, L, M, and cycloviolacin O2 preferentially interacted with model lipid membranes containing phospholipids with phosphatidylethanolamine-headgroups, as measured by surface plasmon resonance. Cyclotide-membrane interactions correlated with cytotoxicity, suggesting that membrane binding underpins cytotoxicity. Overall, this study helps broaden knowledge on the indigenous Indian herb H. enneaspermus, and reports the discovery of novel cyclotides with potent anti-cancer activity.
HostingRepository	PRIDE
AnnounceDate	2020-05-13
AnnouncementXML	Submission_2020-08-11_03:03:40.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Qingdan Du
SpeciesList	scientific name: Hybanthus enneaspermus; NCBI TaxID: 212266;
ModificationList	iodoacetamide derivatized residue
Instrument	TripleTOF 5600

Revision	Datetime	Status	ChangeLog Entry
0	2020-03-06 01:30:02	ID requested
1	2020-05-12 22:25:16	announced
⏵ 2	2020-08-11 03:03:41	announced	2020-08-11: Updated publication reference for PubMed record(s): 32414842.

Du Q, Chan LY, Gilding EK, Henriques ST, Condon ND, Ravipati AS, Kaas Q, Huang YH, Craik DJ, . J Biol Chem, 295(32):10911-10925(2020) [pubmed]

submitter keyword: , peptide chemical synthesis, cyclotide, nuclear magnetic resonance (NMR), cancer cell cytotoxicity, peptide-membrane interaction, anticancer property, surface plasmon resonance (SPR)

David Craik
contact affiliation	Institute for Molecular Bioscience, the University of Queensland, Australia
contact email	d.craik@imb.uq.edu.au
lab head
Qingdan Du
contact affiliation	Institute for Molecular Bioscience
contact email	qingdan.du@imb.uq.edu.au
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD017924
     1. Label: PRIDE project
     2. Name: Discovery and mechanistic studies of cytotoxic cyclotides from the medicinal herb Hybanthus enneaspermus (Linn) F. Muell