Naphthoquinone tryptophan hybrids: A promising small molecule scaffold for mitigating aggregation of amyloidogenic proteins and peptides

Guru Krishna Kumar Viswanathan, Ashim Paul, Ehud Gazit, Daniel Segal

Research output: Contribution to journalReview articlepeer-review

Abstract

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 p-p 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.

Original languageEnglish
Article number242
Pages (from-to)1-10
Number of pages10
JournalFrontiers in Cell and Developmental Biology
Volume7
Issue numberOCT
DOIs
StatePublished - 17 Oct 2019

Keywords

  • Amyloid aggregation
  • Naphthoquinone Tryptophan hybrids
  • Peptides and proteins
  • Self-assembly inhibitors
  • Small molecule

Fingerprint

Dive into the research topics of 'Naphthoquinone tryptophan hybrids: A promising small molecule scaffold for mitigating aggregation of amyloidogenic proteins and peptides'. Together they form a unique fingerprint.

Cite this