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

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 resid...

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Published inCancers Vol. 12; no. 7; p. 1836
Main Authors Ayo, Abiodun, Figueras, Eduard, Schachtsiek, Thomas, Budak, Mazlum, Sewald, Norbert, Laakkonen, Pirjo
Format Journal Article
LanguageEnglish
Published Switzerland MDPI AG 08.07.2020
MDPI
Subjects
Affinity
Alanine
alanine scan
Amino acids
Binding sites
Chromatography
CooP
Drug development
FABP3
Fatty acids
Glioblastoma
Glycine
Ligands
MST
Nanoparticles
Peptides
Phage display
Proteins
Surface plasmon resonance
Xenografts
FABP3
glioblastoma
alanine scan
phage display
CooP
MST
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Summary: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 (K = 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-[Ala ]CooP and A-[Ala ]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-[Ala ]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.
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ISSN:2072-6694
2072-6694
DOI:10.3390/cancers12071836