Nanobody CDR3 peptidomimetica as breast cancer diagnostic

Project Details

Description

Molecular imaging is a non-invasive technique that allows the study of disease-related molecular and cellular events using labeled probes that specifically interact with the biological target of inter-est. A novel class of promising molecular imaging probes consists of Nanobodies (Nbs).1 However, the clinical translation of recombinant proteins, such as Nbs, can be problematic due to immune responses or the extremely high costs associated to their development for human use. Hence, our group focuses on the development of CDR3 loop peptidomimetics of promising Nbs. The human epidermal growth factor receptor type 1 (EGFR/HER1) is a receptor that is highly expressed on the cell membrane of many carcinomas. Starting from Nbs that bind to HER1 (Nb7D12/Nb7C12),2peptide analogues of their respective CDR3 domains have been synthesized. The crystal structure of Nb7D12-HER1 reveals that the CDR3 domain does not adopt a common secondary structure and that Arg30 of the CDR1 domain plays a key role in the binding process.2 To improve the affinity of linear peptide analogues, cyclic CDR3 peptidomimetics bearing a lactam/triazole bridge between residues 105 and 111 were designed. In addition, Gly101 was replaced by Arg.
AcronymFWOAL654
StatusFinished
Effective start/end date1/01/1331/12/16

Keywords

  • Chemistry

Flemish discipline codes

  • Clinical chemistry