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

Ayo, Abiodun; Figueras, Eduard; Schachtsiek, Thomas; Budak, Mazlum; Sewald, Norbert; Laakkonen, Pirjo

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

Ayo A, Figueras E, Schachtsiek T, Budak M, Sewald N, Laakkonen P (2020)
Cancers 12(7): 1836.

Zeitschriftenaufsatz | Veröffentlicht | Englisch

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DOI

https://doi.org/10.3390/cancers12071836

Autor*in

Ayo, Abiodun; Figueras, Eduard; Schachtsiek, Thomas^UniBi; Budak, Mazlum; Sewald, Norbert^UniBi ; Laakkonen, Pirjo

Einrichtung

Fakultät für Chemie > Organische Chemie III
Centrum für Biotechnologie > Arbeitsgruppe N. Sewald

Abstract / Bemerkung

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.

Stichworte

Cancer Research; Oncology

Erscheinungsjahr

2020

Zeitschriftentitel

Cancers

Band

Ausgabe

Art.-Nr.

1836

eISSN

2072-6694

Page URI

https://pub.uni-bielefeld.de/record/2944896

Zitieren

Ayo A, Figueras E, Schachtsiek T, Budak M, Sewald N, Laakkonen P. Tumor-Targeting Peptides: The Functional Screen of Glioblastoma Homing Peptides to the Target Protein FABP3 (MDGI). Cancers. 2020;12(7): 1836.

Ayo, A., Figueras, E., Schachtsiek, T., Budak, M., Sewald, N., & Laakkonen, P. (2020). Tumor-Targeting Peptides: The Functional Screen of Glioblastoma Homing Peptides to the Target Protein FABP3 (MDGI). Cancers, 12(7), 1836. https://doi.org/10.3390/cancers12071836

Ayo, Abiodun, Figueras, Eduard, Schachtsiek, Thomas, Budak, Mazlum, Sewald, Norbert, and Laakkonen, Pirjo. 2020. “Tumor-Targeting Peptides: The Functional Screen of Glioblastoma Homing Peptides to the Target Protein FABP3 (MDGI)”. Cancers 12 (7): 1836.

Ayo, A., Figueras, E., Schachtsiek, T., Budak, M., Sewald, N., and Laakkonen, P. (2020). Tumor-Targeting Peptides: The Functional Screen of Glioblastoma Homing Peptides to the Target Protein FABP3 (MDGI). Cancers 12:1836.

Ayo, A., et al., 2020. Tumor-Targeting Peptides: The Functional Screen of Glioblastoma Homing Peptides to the Target Protein FABP3 (MDGI). Cancers, 12(7): 1836.

A. Ayo, et al., “Tumor-Targeting Peptides: The Functional Screen of Glioblastoma Homing Peptides to the Target Protein FABP3 (MDGI)”, Cancers, vol. 12, 2020, : 1836.

Ayo, A., Figueras, E., Schachtsiek, T., Budak, M., Sewald, N., Laakkonen, P.: Tumor-Targeting Peptides: The Functional Screen of Glioblastoma Homing Peptides to the Target Protein FABP3 (MDGI). Cancers. 12, : 1836 (2020).

Ayo, Abiodun, Figueras, Eduard, Schachtsiek, Thomas, Budak, Mazlum, Sewald, Norbert, and Laakkonen, Pirjo. “Tumor-Targeting Peptides: The Functional Screen of Glioblastoma Homing Peptides to the Target Protein FABP3 (MDGI)”. Cancers 12.7 (2020): 1836.

Daten bereitgestellt von European Bioinformatics Institute (EBI)