Modulation of Amyloidogenic Protein Self-Assembly Using Tethered Small Molecules.

ABSTRACT: Protein-protein interactions (PPIs) are involved in many of life's essential biological functions yet are also an underlying cause of several human diseases, including amyloidosis. The modulation of PPIs presents opportunities to gain mechanistic insights into amyloid assembly, particularly through the use of methods which can trap specific intermediates for detailed study. Such information can also provide a starting point for drug discovery. Here, we demonstrate that covalently tethered small molecule fragments can be used to stabilize specific oligomers during amyloid fibril formation, facilitating the structural characterization of these assembly intermediates. We exemplify the power of covalent tethering using the naturally occurring truncated variant (ΔN6) of the human protein β

SUBMITTER: Cawood EE 

PROVIDER: S-EPMC7729939 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature