UNLABELLED: Peptides are useful tools for directing radioisotopes into tumors. We evaluated the ability of a bacterial peptide display system to isolate new prostate tumor-specific peptides. METHODS: We used the bacterial FliTrx system to identify a new cyclic peptide that binds to prostate carcinoma. Serum stability and binding affinities of the (125)I-labeled peptide were tested. Furthermore, the (131)I-labeled peptide was used to evaluate its biodistribution. RESULTS: Several peptides showing a potential consensus motif were identified. The new peptide MM-2 is stable in serum for up to 24 h. It binds to PC-3 cells, and this binding can be inhibited more than 70% with the unlabeled peptide. Binding to human umbilical vein endothelial cells (HUVECs) and PNT-2 cells is weaker, and competition (27%) in HUVECs is less efficient. The biodistribution showed moderate accumulation in tumor. CONCLUSION: Bacterial peptide display, an alternative to phage peptide display, can allow the identification of specific binding and stable peptides.
UNLABELLED: Peptides are useful tools for directing radioisotopes into tumors. We evaluated the ability of a bacterial peptide display system to isolate new prostate tumor-specific peptides. METHODS: We used the bacterial FliTrx system to identify a new cyclic peptide that binds to prostate carcinoma. Serum stability and binding affinities of the (125)I-labeled peptide were tested. Furthermore, the (131)I-labeled peptide was used to evaluate its biodistribution. RESULTS: Several peptides showing a potential consensus motif were identified. The new peptide MM-2 is stable in serum for up to 24 h. It binds to PC-3 cells, and this binding can be inhibited more than 70% with the unlabeled peptide. Binding to human umbilical vein endothelial cells (HUVECs) and PNT-2 cells is weaker, and competition (27%) in HUVECs is less efficient. The biodistribution showed moderate accumulation in tumor. CONCLUSION: Bacterial peptide display, an alternative to phage peptide display, can allow the identification of specific binding and stable peptides.
Authors: Regine García Boy; Walter Mier; Eva Maria Nothelfer; Annette Altmann; Michael Eisenhut; Harald Kolmar; Michael Tomaszowski; Susanne Krämer; Uwe Haberkorn Journal: Mol Imaging Biol Date: 2009-11-24 Impact factor: 3.488