Molecular Innovations Toward Theranostics of Aggressive Prostate Cancer

Abstract

The effort explores the preparation theranostics comprising a therapeutic peptide and a chelating group based on DOTA. Methods to develop a series of dendrimers bearing an imaging group at the core evolved from late-stage alkyne functionalization to early incorporation of the imaging group. Efforts showed that dendrimers of varying sizes can be accessed with this strategy. Methods for the accelerated synthesis of these targets were developed. Solubility parameters were also defined. Methods to incorporate multiple copies of a therapeutic peptide rested on the utilization of linkers that were either biolabile or stable. Efforts with biolabile linkers revealed a new class of hydrazones that show promise in multiple areas of therapeutic research, although more limited utility to date with highly soluble cargos (the peptide of interest). Efforts with stable linkers included maleimide and therapeutics bearing a thiol (cysteine) and covalent ligation resulting from selective triazine addition of a functionalized therapeutic. The latter strategy is favored based on the instability of the maleimide and the need for long reaction times.

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Document Details

Document Type
Technical Report
Publication Date
Sep 01, 2016
Accession Number
AD1038997

Entities

People

  • Eric E Simanek

Organizations

  • Texas Christian University

Tags

Communities of Interest

  • Biomedical

DTIC Thesaurus Topics

  • Amino Acids
  • Anti-Infective Agents
  • Chemical Compounds
  • Chemical Synthesis
  • Chemistry
  • Density Functional Theory
  • Hydrazines
  • Macromolecules
  • Mass Spectrometry
  • Materials Science
  • Molecular Dynamics
  • Molecules
  • Organic Chemistry
  • Polymer Chemistry
  • Polymers
  • Prostate Cancer
  • Therapy

Readers

  • Molecular and Cellular Biochemistry
  • Oncology
  • Organic Chemistry