Macrocyclization between head, tail or sidechains is a frequently employed strategy to enhance peptide and peptidomimetic stability, selectivity and affinity.

No abstract

The function of the large excess free FXIII-B circulating in plasma is not known.• We show that free FXIII-B does not interact with the complement system.• α 2 -macroglobulin remains a candidate binding partner to free FXIII-B.

Among the many molecular entities suitable for therapeutic use, peptides have emerged as a particularly attractive option for academic drug discovery and development. Their modular structure and extendibility, the availability of powerful and affordable screening platforms, and the relative ease-of-synthesis render therapeutic peptides highly approachable for teaching and research alike. With a strong focus on the therapeutic modulation of host defence pathways, including the complement and renin-angiotensin systems, the Molecular Pharmacy group at the University of Basel strongly relies on peptides to introduce students to practical aspects of modern drug design, to discover novel therapeutics for immune and inflammatory diseases, and to expand on options for the preclinical development of a promising drug class. Current projects reach from student-driven iterative design of peptidic angiotensin-converting enzyme inhibitors and the use of phage display technology to discover novel immune modulators to the development of protective peptide coatings for biomaterials and transplants and the structure-activity-relationship-guided optimization of therapeutic peptide drug candidates in late-stage clinical trials. Even at the current stage, peptides allow for a perfect circle between pharmaceutical research and education, and the recent spark of clinical applications for peptide-based drugs may only increase the value and relevance of this versatile drug class.

IgA nephropathy (IgAN) is the most common glomerular autoimmune disease and has severe long‐term consequences for patients, with 40% of the patients eventually progressing to end‐stage renal disease. Despite the severity, no causal treatment is currently available. While the pathogenesis of IgAN is complex, disease severity is linked to autoantibodies against the gd‐IgA1 epitope, a stretch in the hinge region of IgA1 that lacks O‐glycans and is found in the characteristic immune complexes deposited in the kidneys of IgAN patients. One elegant, causal approach would be to remove the anti‐gd‐IgA1 autoantibodies and consequently reduce the immune complex burden on the kidneys. The administration of synthetic polymers that present autoantigens in a multivalent manner have been established as promising therapeutic strategies in other autoimmune diseases and may be applied to IgAN. We here present an improved protocol for the synthesis of the gd‐IgA1 epitope, its successful coupling to a poly‐L‐lysine polymer and proof‐of‐concept experiments that the polymer‐bound synthetic glycopeptide is able to capture the IgAN autoantibodies, making this approach a promising way forward for developing a targeted treatment option for IgAN patients.