Leveraging Bio-Inspired Molecules for Cancer Theranostics
type: CreativeWork
description: A variety of molecules can be radiolabeled and delivered to a cancer site for the purposes of diagnostics and therapy. Among the most promising of tumor targeting molecules are peptides and antibodies. These bio-inspired molecules can be designed and synthesized to target and respond to cancer cells based on the properties of those cells. Matrix metalloproteinase (MMP) enzymes are over-expressed by some metastatic cancers, in which they are responsible for the degradation and remodeling of the extracellular matrix. In recent years, MMPs have emerged as promising targets for enzyme-responsive diagnostic probes because oligopeptides can be designed to be selectively hydrolyzed by exposure to these enzymes. With the ultimate goal of developing radio-iodinated peptides as supramolecular building blocks for MMP-sensitive tools for nuclear imaging and therapy, we designed three MMP-9-responsive peptides containing either tyrosine or iodotyrosine, in order to assess the impact of iodotyrosine introduction to peptide structure and cleavage kinetics. We found that the peptides containing iodotyrosine underwent more rapid and more complete hydrolysis by MMP-9. While the peptides under investigation were predominantly disordered, it was found that iodination increased the degree of aromatic residue-driven aggregation of the peptides. We determined that these iodination-related trends stem from improved overall intramolecular order through H- and halogen bonding, in addition to intermolecular organization of the self-assembled peptides due to steric and electrostatic effects introduced by the halogenated tyrosine. In addition to the influence of iodination on peptide enzyme response, amino acid substitutions can have a profound effect on how peptide sequences interact with one another and are enzymatically hydrolyzed. In conducting an analysis of promising sequences for translation into MMP-activated imaging probes, we identified a three-residue modification of an 11-amino acid…
abstract: A variety of molecules can be radiolabeled and delivered to a cancer site for the purposes of diagnostics and therapy. Among the most promising of tumor targeting molecules are peptides and antibodies. These bio-inspired molecules can be designed and synthesized to target and respond to cancer cells based on the properties of those cells. Matrix metalloproteinase (MMP) enzymes are over-expressed by some metastatic cancers, in which they are responsible for the degradation and remodeling of the extracellular matrix. In recent years, MMPs have emerged as promising targets for enzyme-responsive diagnostic probes because oligopeptides can be designed to be selectively hydrolyzed by exposure to these enzymes. With the ultimate goal of developing radio-iodinated peptides as supramolecular building blocks for MMP-sensitive tools for nuclear imaging and therapy, we designed three MMP-9-responsive peptides containing either tyrosine or iodotyrosine, in order to assess the impact of iodotyrosine introduction to peptide structure and cleavage kinetics. We found that the peptides containing iodotyrosine underwent more rapid and more complete hydrolysis by MMP-9. While the peptides under investigation were predominantly disordered, it was found that iodination increased the degree of aromatic residue-driven aggregation of the peptides. We determined that these iodination-related trends stem from improved overall intramolecular order through H- and halogen bonding, in addition to intermolecular organization of the self-assembled peptides due to steric and electrostatic effects introduced by the halogenated tyrosine. In addition to the influence of iodination on peptide enzyme response, amino acid substitutions can have a profound effect on how peptide sequences interact with one another and are enzymatically hydrolyzed. In conducting an analysis of promising sequences for translation into MMP-activated imaging probes, we identified a three-residue modification of an 11-amino acid…
author: MacPherson, Douglas S
keywords: Amino Acids, Peptides, and Proteins, Biochemistry, Biotechnology, Enzymes and Coenzymes, Medicinal Chemistry and Pharmaceutics, Nanotechnology, Pharmaceutical Preparations, Therapeutics, Translational Medical Research, peptides, enzyme-responsive materials, radiotherapy, matrix metalloproteinase, dual-variable domain antibody, site-specific bioconjugation
date published: 2023-02-01T08:00:00Z
date modified: 2026-07-24T01:59:38Z
provider: City University of New York - Graduate Center
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: The Graduate School and University Center of The City University of New York