PXD029126-1

PXD029126 is an original dataset announced via ProteomeXchange.

Title	Redesigned peptide-based LDH5 inhibitors enter cancer cells efficiently and impair proliferation
Description	Lactate dehydrogenase 5 (LDH5), an enzyme overexpressed in many cancers, is an attractive target for anticancer therapy. Recently, we successfully designed an LDH5 peptide inhibitor, cGmC9, by targeting protein-protein interactions required for LDH5 enzymatic activity. LDH5 is expressed in the cytosol, therefore this peptide inhibitor has to enter cancer cells to hit its target. In this study we designed cGmC9 analogues and evaluated their internalisation, membrane toxicity, and antiproliferative activity against a panel of cancer cell lines with distinct metabolic profiles. Lead analogue [R/r]cGmC9 showed low toxicity and impaired proliferation in triple negative breast cancer cells, and proteomics analysis showed expected compensatory metabolic changes in response to LDH5 inhibition. These results confirm that LDH5 peptide inhibitors enter cancer cells, reach their cytosol, inhibit LDH5 activity and kill glycolytic tumour cells. Small-molecule drugs have been developed to target the substrate/cofactor sites of LDH5, but none has reached the clinic to date due to cross-reactivity associated with targeting NADH binding site, or low potency in vivo associated with poor stability and poor membrane permeability. This is the first study demonstrating ability of a designed peptide to inhibit LDH5 activity in cancer cells, and confirms the potential of using peptides as inhibitors of intracellular protein-protein interactions relevant for cancer pathways.
HostingRepository	PRIDE
AnnounceDate	2025-05-06
AnnouncementXML	Submission_2025-05-06_09:04:31.667.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Andrew Lai
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	TripleTOF 5600

Revision	Datetime	Status	ChangeLog Entry
0	2021-10-14 07:58:58	ID requested
⏵ 1	2025-05-06 09:04:32	announced

Nadal-Buf, í F, Chan LY, Mohammad HH, Mason JM, Salomon C, Lai A, Thompson EW, Craik DJ, Kaas Q, Henriques ST, Peptide-based LDH5 inhibitors enter cancer cells and impair proliferation. Cell Mol Life Sci, 79(12):606(2022) [pubmed]

10.1007/s00018-022-04633-3;

submitter keyword: peptide inhibitors,Lactate dehydrogenase

Carlos Salomon
contact affiliation	Head, Exosome Biology Laboratory, Centre for Clinical Diagnostics, UQ Centre for Clinical Research, University of Queensland, Australia
contact email	c.salomongallo@uq.edu.au
lab head
Andrew Lai
contact affiliation	University of Queensland
contact email	a.lai@uq.edu.au
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2025/05/PXD029126

PRIDE project URI

• PRIDE
  1. PXD029126
     1. Label: PRIDE project
     2. Name: Redesigned peptide-based LDH5 inhibitors enter cancer cells efficiently and impair proliferation