We hypothesized that hybrid molecules that combine apoptosis-dependent and apoptosis-independent mode of actions in a single molecule may lead to enhanced antitumor activity.
Genetic engineering has led to the development of fusion protein toxins, which are targeted effector molecules that combine a targeting ligand such as a growth factor with a cytocidal moiety such as a plant or bacterial toxin.
The structure of LHA at 2.6 Å reported here provides an understanding of the structural implications and challenges of engineering therapeutic molecules that combine functional properties of LHn of BoNTs with specific ligand partners to target different cell types.
Another exciting recent strategy involves the development of single-peptide molecules that combine differing modes of action.
Considering the structural and functional similarity of EC and 15d-PGJ2, we also tested a series of chimeric molecules that combined features of EC and 15d-PGJ2, the synthesis of which is described in detail elsewhere (Egger et al, 2014).
Desensitization and endocytosis of G-protein-coupled receptors following the agonist binding are mediated by β-arrestins, which function as adaptor molecules that combine E3 ubiquitin ligases with the receptors to ubiquitinate the receptors (Shenoy and Lefkowitz, 2011).
