Efficacy of peptide nucleic acid and selected conjugates against specific cellular pathologies of amyotrophic lateral sclerosis

Elisse C Browne; Sonam Parakh; Luke F Duncan; Steven J Langford; Julie D Atkin; Belinda M Abbott

doi:10.1016/j.bmc.2016.02.022

Efficacy of peptide nucleic acid and selected conjugates against specific cellular pathologies of amyotrophic lateral sclerosis

Bioorg Med Chem. 2016 Apr 1;24(7):1520-7. doi: 10.1016/j.bmc.2016.02.022. Epub 2016 Feb 18.

Authors

Elisse C Browne¹, Sonam Parakh², Luke F Duncan¹, Steven J Langford³, Julie D Atkin², Belinda M Abbott⁴

Affiliations

¹ Department of Chemistry and Physics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne 3086, Australia.
² Department of Biochemistry and Genetics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne 3086, Australia; Department of Biomedical Sciences, Faculty of Medicine and Health Science, Macquarie University, Sydney 2109, Australia.
³ School of Chemistry, Monash University, Clayton 3800, Australia.
⁴ Department of Chemistry and Physics, La Trobe Institute for Molecular Science, La Trobe University, Melbourne 3086, Australia. Electronic address: b.abbott@latrobe.edu.au.

PMID: 26935939
DOI: 10.1016/j.bmc.2016.02.022

Abstract

Cellular studies have been undertaken on a nonamer peptide nucleic acid (PNA) sequence, which binds to mRNA encoding superoxide dismutase 1, and a series of peptide nucleic acids conjugated to synthetic lipophilic vitamin analogs including a recently prepared menadione (vitamin K) analog. Reduction of both mutant superoxide dismutase 1 inclusion formation and endoplasmic reticulum stress, two of the key cellular pathological hallmarks in amyotrophic lateral sclerosis, by two of the prepared PNA oligomers is reported for the first time.

Keywords: Amyotrophic lateral sclerosis; Peptide nucleic acid; Vitamin conjugation.

Publication types

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

MeSH terms

Amyotrophic Lateral Sclerosis / drug therapy*
Amyotrophic Lateral Sclerosis / genetics
Amyotrophic Lateral Sclerosis / metabolism
Amyotrophic Lateral Sclerosis / pathology*
Animals
Cells, Cultured
Endoplasmic Reticulum Stress / drug effects*
Mice
Peptide Nucleic Acids / chemical synthesis
Peptide Nucleic Acids / chemistry
Peptide Nucleic Acids / pharmacology*
Superoxide Dismutase / deficiency
Superoxide Dismutase / genetics
Superoxide Dismutase / metabolism*
Superoxide Dismutase-1
Thermodynamics
Vitamins / chemistry
Vitamins / pharmacology*

Substances

Peptide Nucleic Acids
Vitamins
Superoxide Dismutase
Superoxide Dismutase-1