Peptidic Inhibitors of N-myc for Treatment of Neuroblastoma

Abstract

The goal of this project is to develop drug-like peptides that can directly bind to the oncogenic transcription factor N-myc and block its ability to activate downstream genes. N-myc, an oncogenic transcription factor, is an attractive target for the treatment of Neuroblastoma. However, N-myc is thought to be an undruggable target as it is involved in protein-protein interactions that are difficult to modulate with small molecules. Here, we attempted to develop drug-like peptides that can directly bind to N-myc and block its activation of downstream genes. In the past year, we have attempted to use mRNA display, an in vitro selection technology, to develop short peptides that can bind to N-myc. We originally identified in several sequences resulting from an invitro selection targeting N-myc via next generation seqeuncing, however, subsequent experiments have determined that the peptides resulting from this selection can unexpectedly bind the matrix used for target immobilization, even in the presence of biotin. Our results also demonstrate the importance of using a hydrophilic immobilization matrix to avoid a strong undesirable hydrophobic bias in the library.

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Document Details

Document Type
Technical Report
Publication Date
Dec 01, 2018
Accession Number
AD1086023

Entities

People

  • Richard W. Roberts
  • Terry T. Takahashi

Organizations

  • University of Southern California

Tags

DTIC Thesaurus Topics

  • Amino Acids
  • Engineers
  • Genetic Structures
  • Hydrophilic Properties
  • Hydrophobic Properties
  • Inhibitors
  • Laboratory Equipment
  • Molecules
  • Neuroblastoma
  • Protein-Protein Interactions
  • Proteins
  • Sequences
  • Small Molecules
  • Students
  • Targeting
  • Targets
  • Transcription Factors

Fields of Study

  • Biology

Readers

  • Marksmanship and Weaponry.
  • Molecular and Cellular Biochemistry
  • Oncology