1. Tumor-Targeting Peptides : The Functional Screen of Glioblastoma Homing Peptides to the Target Protein FABP3 (MDGI)
- Author
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Thomas Schachtsiek, Eduard Figueras, Abiodun Ayo, Mazlum Budak, Pirjo Laakkonen, Norbert Sewald, CAN-PRO - Translational Cancer Medicine Program, Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki Institute of Life Science HiLIFE, Infra, Pirjo Maarit Laakkonen / Principal Investigator, and HUS Helsinki and Uusimaa Hospital District
- Subjects
0301 basic medicine ,Cancer Research ,Phage display ,FABP3 ,3122 Cancers ,P32/GC1QR ,Peptide ,02 engineering and technology ,lcsh:RC254-282 ,Article ,03 medical and health sciences ,In vivo ,Alanine ,chemistry.chemical_classification ,MST ,Microscale thermophoresis ,CooP ,glioblastoma ,alanine scan ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,021001 nanoscience & nanotechnology ,LIBRARIES ,In vitro ,3. Good health ,Amino acid ,030104 developmental biology ,chemistry ,Biochemistry ,Oncology ,GROWTH ,Target protein ,phage display ,DISPLAY ,0210 nano-technology - 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 µ, 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-[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&ndash, A-CooP interaction that may be important for future applications of drug conjugate design and development.
- Published
- 2020