1. Academic Validation
  2. Tumor-Targeting Peptides: The Functional Screen of Glioblastoma Homing Peptides to the Target Protein FABP3 (MDGI)

Tumor-Targeting Peptides: The Functional Screen of Glioblastoma Homing Peptides to the Target Protein FABP3 (MDGI)

  • Cancers (Basel). 2020 Jul 8;12(7):1836. doi: 10.3390/cancers12071836.
Abiodun Ayo 1 Eduard Figueras 2 Thomas Schachtsiek 2 Mazlum Budak 2 Norbert Sewald 2 Pirjo Laakkonen 1 3
Affiliations

Affiliations

  • 1 Translational Cancer Medicine Research Program, Faculty of Medicine, University of Helsinki, 00014 Helsinki, Finland.
  • 2 Organic and Bioorganic Chemistry OC III, Department of Chemistry, Bielefeld University, 33615 Bielefeld, Germany.
  • 3 Laboratory Animal Center, Helsinki Institute of Life Science (HiLIFE), University of Helsinki, 00014 Helsinki, Finland.
Abstract

We recently identified the glioblastoma homing peptide CooP (CGLSGLGVA) using in vivo phage display screen. The mammary-derived growth inhibitor (MDGI/FABP3) was identified as its interacting partner. Here, we present an alanine scan of A-CooP to investigate the contribution of each amino acid residue to the binding to FABP3 by microscale thermophoresis (MST) and surface plasmon resonance (SPR). We also tested the binding affinity of the A-CooP-K, KA-CooP, and retro-inverso A-CooP analogues to the recombinant FABP3. According to the MST analysis, A-CooP showed micromolar (KD = 2.18 µM) affinity to FABP3. Alanine replacement of most of the Amino acids did not affect peptide affinity to FABP3. The A-CooP-K variant showed superior binding affinity, while A-[Ala5]CooP and A-[Ala7]CooP, both replacing a glycine residue with alanine, showed negligible binding to FABP3. These results were corroborated in vitro and in vivo using glioblastoma models. Both A-CooP-K and A-CooP showed excellent binding in vitro and homing in vivo, while A-[Ala5]CooP and control Peptides failed to bind the cells or home to the intracranial glioblastoma xenografts. These results provide insight into the FABP3-A-CooP interaction that may be important for future applications of drug conjugate design and development.

Keywords

CooP; FABP3; MST; alanine scan; glioblastoma; phage display.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-P4115
    Glioblastoma-Targeting Nonapeptide