Design of sunflower trypsin inhibitor 1 derived probes targeting the LDLR and evaluation of their brain delivery
) of ∼0.01 (∼10-fold less than that of SFTI-1). We present workflows for structure- and interaction prediction model-informed medicinal chemistry on natural circular peptides for the development of molecular shuttle systems. Our results suggest that active receptor-mediated transport (RMT) was achieved in vitro; however, in vivo transport experiments indicated dominant efflux at the BBB counteracting active uptake, highlighting the challenges in translational work arising from the use of imperfect in vitro screening systems and subsequent in vivo proof-of-concept models.
Authors
- Irena Loryan (ORCID: https://orcid.org/0000-0002-1557-4416)
- Benjamí Oller‐Salvia (ORCID: https://orcid.org/0000-0002-8140-6111)
- Roland Hellinger (ORCID: https://orcid.org/0000-0002-8955-8793)
- Maria C. Lucana (ORCID: https://orcid.org/0009-0006-1680-3483)
- Christian W. Gruber (ORCID: https://orcid.org/0000-0001-6060-7048)
- Aghavni Ginosyan
- Jonathan Dieringer
- Paula Schwarz
- Kirtikumar B. Jadhav
Institutions
- Uppsala University (SE)
- University of Vienna (AT)
- TU Wien (AT)
- Institut Químic de Sarrià (ES)
- Medical University of Vienna (AT)
Publication Details
- Journal
- Biomedicine & Pharmacotherapy
- Published
- 2026-07-30
- DOI
- https://doi.org/10.1016/j.biopha.2026.119756
- Primary Topic
- Biochemical and Structural Characterization
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- European Cooperation in Science and Technology
- Austrian Science Fund
- Erasmus+