Novel binders derived from an albumin-binding domain scaffold targeting Prostate Secretory Protein-94

Lucie Marečková¹, Hana Petroková¹, Milan Kuchař¹, Jiří Černý² and Petr Malý¹

¹Laboratory of Ligand Engineering and ²Laboratory of Biomolecular Recognition, Institute of Biotechnology AS CR, v. v. i. Vídeňská 1083, 142 20 Prague, Czech Republic

Contact: lucie.mareckova@img.cas.cz, petr.maly@img.cas.cz

PSP-94, also known as β-microseminoprotein (MSMB), is a small cysteine-rich protein, mainly found in human seminal plasma. Recently it has been well documented that the expression of PSP-94 is decreasing during the development of prostate cancer (PC). Currently used test for PC diagnosis relies on the detection of serum level of PSA (prostate-specific antigen known also as KLK3) in ELISA but this examination is insufficient due to high numbers of false positives leading to a useless therapeutic intervention, i.e. risky and high-cost prostate biopsies. The principle problem is that diagnosis of high levels of PSA does not well distinguish between a malignant form and benign prostate hyperplasia. Therefore, the development of tools for more precise assessment of PC biomarkers in blood serum can significantly improve the accuracy and validity of the novel diagnostics. Besides standard commercial one-type antibody–based ELISA test for PC exploration, a biosensor with multiple biomarkers might be a promising solution. We plan, therefore, to develop novel binders raised against human PSP-94 seminal fluid protein biomarker. While for KLK-family members the increase in serum levels might be an indicator of PC progression, a combination with serum level decrease for PSP-94 can be confirmative. The aim of this study was to generate novel binders (called PAB variants), derived from albumin-binding domain scaffold, targeting human PSP-94 protein and to select them using ribosome display approach. We demonstrate here that from the collection of 34 sequence-verified clones, seven candidates PAB019, PAB036, PAB037, PAB042, PAB044, PAB046 and PAB050 were identified as promising binders of human PSP-94 and currently are being characterized in more detail.

Funding by the grant FR-TI4/667 MPO ČR and the institutional research concept AV0Z5052070.