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Identification of novel prostate-specific antigen-binding peptides modulating its enzyme activity
- Source :
- European Journal of Biochemistry. 267:6212-6220
- Publication Year :
- 2000
- Publisher :
- Wiley, 2000.
-
Abstract
- Prostate-specific antigen (PSA) is a serine protease with highly prostate-specific expression. Measurement of PSA in serum is widely used for diagnosis and monitoring of prostate cancer. PSA dissolves the seminal gel forming after ejaculation. It has been suggested to mediate invasion and metastasis of prostate cancer but also to exert antiangiogenic activity. We have identified peptides specific for PSA by screening cyclic phage display peptide libraries. PSA-binding peptides were isolated from four different libraries and produced as a fusion protein with glutathione S-transferase (GST). The phage and fusion proteins were shown to bind to PSA specifically as indicated by lack of binding to other serine proteinases. A peptide with four cysteines showed the highest affinity for PSA. Zn2+, an inhibitor of PSA activity, increased the affinity of the peptides to PSA. The binding specificity was characterized by cross-inhibition using monoclonal anti-PSA antibodies of known epitope specificities. The peptides bound to the same region as mAbs specific for free PSA indicating that they bind close to the active site of the enzyme. The peptides enhanced the enzyme activity of PSA against a chromogenic substrate. These results show that peptides binding to PSA and modulating its enzyme activity can be developed by phage display technique. The peptides have the potential to be used for identification of PSA variants and for imaging and targeting of prostatic tumors.
- Subjects :
- chemistry.chemical_classification
0303 health sciences
Phage display
Peptide
Biology
urologic and male genital diseases
Biochemistry
Fusion protein
Molecular biology
Cyclic peptide
Epitope
3. Good health
03 medical and health sciences
Prostate-specific antigen
Enzyme activator
0302 clinical medicine
chemistry
Antigen
030220 oncology & carcinogenesis
030304 developmental biology
Subjects
Details
- ISSN :
- 00142956
- Volume :
- 267
- Database :
- OpenAIRE
- Journal :
- European Journal of Biochemistry
- Accession number :
- edsair.doi...........9c54ad14e696237e21dd6955057875ef