title: Screening and characterization of novel specific peptides targeting MDA-MB-231 claudin-low breast carcinoma by computer-aided phage display methodologies.
abstract: Claudin-low breast carcinoma represents 19% of all breast cancer cases and is characterized by an aggressive progression with metastatic nature and high rates of relapse. Due to a lack of known specific molecular biomarkers for this breast cancer subtype, there are no targeted therapies available, which results in the worst prognosis of all breast cancer subtypes. Hence, the identification of novel biomarkers for this type of breast cancer is highly relevant for an early diagnosis. Additionally, claudin-low breast carcinoma peptide ligands can be used to design powerful drug delivery systems that specifically target this type of breast cancer.
  
  
  
  In this work, we propose the identification of peptides for the specific recognition of MDA-MB-231, a cell line representative of claudin-low breast cancers, using phage display (both conventional panning and BRASIL). Binding assays, such as phage forming units and ELISA, were performed to select the most interesting peptides (i.e., specific to the target cells) and bioinformatics approaches were applied to putatively identify the biomarkers to which these peptides bind.
  
  
  
  Two peptides were selected using this methodology specifically targeting MDA-MB-231 cells, as demonstrated by a 4 to 9 log higher affinity as compared to control cells. The use of bioinformatics approaches provided relevant insights into possible cell surface targets for each peptide identified.
  
  
  
  The peptides herein identified may contribute to an earlier detection of claudin-low breast carcinomas and possibly to develop more individualized therapies.
authors.affiliation: Centre of Biological Engineering (CEB), University of Minho, Campus de Gualtar, 4710-057, Braga, Portugal.
authors.forename: Franklin L
authors.initials: FL
authors.lastname: Nobrega
authors.affiliation: Centre of Biological Engineering (CEB), University of Minho, Campus de Gualtar, 4710-057, Braga, Portugal.
authors.forename: Débora
authors.initials: D
authors.lastname: Ferreira
authors.affiliation: Centre of Biological Engineering (CEB), University of Minho, Campus de Gualtar, 4710-057, Braga, Portugal.
authors.forename: Ivone M
authors.initials: IM
authors.lastname: Martins
authors.affiliation: Laboratory of Systems and Synthetic Biology, Wageningen University and Research Centre, Stippeneng 4, 6708WE, Wageningen, The Netherlands.
authors.forename: Maria
authors.initials: M
authors.lastname: Suarez-Diez
authors.affiliation: Centre of Biological Engineering (CEB), University of Minho, Campus de Gualtar, 4710-057, Braga, Portugal.
authors.forename: Joana
authors.initials: J
authors.lastname: Azeredo
authors.affiliation: Centre of Biological Engineering (CEB), University of Minho, Campus de Gualtar, 4710-057, Braga, Portugal.
authors.forename: Leon D
authors.initials: LD
authors.lastname: Kluskens
authors.affiliation: Centre of Biological Engineering (CEB), University of Minho, Campus de Gualtar, 4710-057, Braga, Portugal. lrmr@deb.uminho.pt.
authors.forename: Lígia R
authors.initials: LR
authors.lastname: Rodrigues
mesh_terms: D000595:Amino Acid Sequence; D014408:Biomarkers, Tumor; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D061505:Cell Surface Display Techniques; D057167:Claudins / Q000235:genetics / Q000378:metabolism*; D019295:Computational Biology / Q000379:methods; D005260:Female; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation
chemical_list: D014408:Biomarkers, Tumor; D057167:Claudins; D008024:Ligands; D019151:Peptide Library; D010455:Peptides
keywords: Claudin-low breast cancer; DTFNSFGRVRIE; MDA-MB-231; PRWAVSP; Phage display