Naphthoquinone Tryptophan hybrids: A promising small molecule scaffold for mitigating aggregation of amyloidogenic proteins and peptides
- 1Tel Aviv University, Israel
A current challenge faced by researchers is the lack of disease-modifying therapeutics for amyloid formation that is associated with several human diseases. Although the monomeric proteins or peptides involved in various amyloidogenic diseases do not have amino acid sequence homology, there appears to be a structural correlation among the amyloid assemblies, which are responsible for distinct pathological conditions. Here, we review our work on Naphthoquinone Tryptophan (NQTrp) hybrids, a small molecule scaffold that can generically modulate neuronal and non-neuronal amyloid aggregation both in vitro and in vivo. NQTrp reduces the net amyloid load by inhibiting the process of amyloid formation and disassembling the pre-formed fibrils, both in a dose-dependent manner. As a plausible mechanism of action, NQTrp effectively forms hydrogen bonding and hydrophobic interactions, such as π-π stacking, with the vital residues responsible for the initial nucleation of protein/peptide aggregation. This review highlights the effectiveness of the NQTrp hybrid scaffold for developing novel small molecule modulators of amyloid aggregation.
Keywords: amyloid aggregation, Naphthoquinone Tryptophan hybrids, Peptides and proteins, Self-assembly inhibitors, small molecule
Received: 26 May 2019;
Accepted: 02 Oct 2019.
Copyright: © 2019 Viswanathan, Paul, Gazit and Segal. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Prof. Daniel Segal, Tel Aviv University, Tel Aviv, Israel, firstname.lastname@example.org