CeNT Seminar (28.11.2025): Self-assembly of Therapeutic Peptides

Peptides are a major class of therapeutic agents which have high potency and specificity. However, there can be issues as many are prone to self-assembly into fibrillar species, or amorphous aggregates.  These days it is also very common for the peptides to be modified in some way, such as lipidated, in order to extend their half-lives in vivo. The lipidation greatly affects the self-assembly processes and a diverse range of oligomeric species can be formed depending upon lipidation site and also the lipid moiety itself.  The self-assembly of lipidated and non-lipidated variants of GLP-1 (including analogues of some of the Ozempic-type drugs). In these cases, self assembly can be both beneficial or deleterious depending upon the state which is populated.  For a different type of therapeutic agent, gonadotropin releasing hormone antagonists, the self assembly into amyloid-like fibrils and also micro-crystalline suspensions are essential for its formulation, delivery and action in vivo. Recent research on understanding the mechanism by which these different self-assembled states are formed will be discussed.

References:

1. Observation of unique stable nano-assemblies of a lipidated glucagon-like peptide 1 analogue.  Prada Brichtova E, Gomes Dos Santos AL, Jackson SE. (2025) Soft Matter. In press. Effect of Lipidation on the Structure, Oligomerization, and Aggregation of Glucagon-like Peptide 2. Přáda Brichtová E, Edu IA, Li X, Becher F, Gomes Dos Santos AL, Jackson SE. Bioconjug Chem (2025 ) Mar 19;36(3):401-414.

3. Li, Xinyang; Serpell, Louise; Bukrinski, Jens; Boutignon, François; Maclean, Carol; Jackson, Sophie. Mechanism of Self-assembly of the Gonadropin Releasing Hormone Antagonist Teverelix into Amyloid Fibrils (2025) Molecular Pharmaceutics. In press.