Targeting anti-apoptotic Bcl2 proteins with scyllatoxin-based BH3 domain mimetics

M Margaret Harris; Zachary Coon; Najah Alqaeisoom; Brian Swords; Justin M Holub

doi:10.1039/c5ob02080h

Targeting anti-apoptotic Bcl2 proteins with scyllatoxin-based BH3 domain mimetics

Org Biomol Chem. 2016 Jan 14;14(2):440-446. doi: 10.1039/c5ob02080h.

Authors

M Margaret Harris¹, Zachary Coon, Najah Alqaeisoom, Brian Swords, Justin M Holub

Affiliation

¹ Department of Chemistry and Biochemistry, Ohio University, Athens, OH 45701, USA. holub@ohio.edu.

PMID: 26563651
DOI: 10.1039/c5ob02080h

Abstract

BH3 domain mimetics based on the small protein scyllatoxin (ScTx) were designed to target the anti-apoptotic protein Bcl2 in vitro. Intrinsically disordered ScTx variants were found to bind Bcl2 with nanomolar affinity, indicating that an induced fit binding mechanism is required for favorable BH3 : Bcl2 interaction.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Biomimetic Materials / chemical synthesis
Biomimetic Materials / chemistry*
Biomimetic Materials / pharmacology*
Drug Design*
Models, Molecular
Protein Binding
Protein Structure, Tertiary
Proto-Oncogene Proteins c-bcl-2 / antagonists & inhibitors*
Proto-Oncogene Proteins c-bcl-2 / chemistry
Proto-Oncogene Proteins c-bcl-2 / metabolism*
Scorpion Venoms / chemistry*
Scorpion Venoms / metabolism

Substances

Proto-Oncogene Proteins c-bcl-2
Scorpion Venoms
leiurotoxin I