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

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http://hdl.handle.net/10138/319289

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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 , vol. 12 , no. 7 , 1836 . https://doi.org/10.3390/cancers12071836

Title: Tumor-Targeting Peptides : The Functional Screen of Glioblastoma Homing Peptides to the Target Protein FABP3 (MDGI)
Author: Ayo, Abiodun; Figueras, Eduard; Schachtsiek, Thomas; Budak, Mazlum; Sewald, Norbert; Laakkonen, Pirjo
Contributor: University of Helsinki, CAN-PRO - Translational Cancer Medicine Program
University of Helsinki, Helsinki Institute of Life Science HiLIFE, Infra
Date: 2020-07
Language: eng
Number of pages: 19
Belongs to series: Cancers
ISSN: 2072-6694
URI: http://hdl.handle.net/10138/319289
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 (K-D= 2.18 mu M) 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(5)]CooP and A-[Ala(7)]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(5)]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.
Subject: glioblastoma
FABP3
CooP
MST
alanine scan
phage display
P32/GC1QR
LIBRARIES
DISPLAY
GROWTH
3122 Cancers
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