Probing the Matrix

Since the matrix metalloproteinases (MMPs) are involved in the degradation and turnover of many components of the extracellular matrix (ECM) of a cell,1 it makes sense that they would be a target for cancer treatment and tumor imaging. There are 23 different MMPs in humans and they are closely related.  This close relation creates challenges in finding specific substrates, since a single substrate may be cleaved by several MMP enzymes, due to overlapping specificities. As reported in Biomaterials Science, a team, led by Lu Sun, designed a fluorescent nanoprobe that is highly selective for MMP-2. They selected MMP-2 since it was overexpressed in the tumor cells of interest, as well as for its ability to access the cleavage site. They designed their probe by combining a fluorescent fusion protein, a cell-penetrating peptide (CPP), the MMP-2 cleavage site, and immobilized it by chelation to a nickel ferrite nanoparticle surface. In order to measure activation of the probe by tumor-secreted MMP-2, a cell assay was performed with a FRET peptide, MOCAc-Pro-Leu-Gly-Leu-A2pr(Dnp)-Ala-Arg-NH2 (MOC-3163-v). The assay confirmed that their selective nanoprobe was only activated by MMP-2.The strategy could pave the way for new, selective MMP probes for use in intracellular tumor imaging.2

Reference:

  1. D. Rodríguez et al., Biochimica et Biophysica Acta, 1803 (1), 39 (2010).
  2. L. Sun et al., Biomater. Sci., (2018). Advance Article
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Denise Karounos

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Denise Karounos joined Peptides International in October 2016. After completing her BS in chemistry from West Virginia University, she spent time as an organic chemist at Bachem Bioscience synthesizing peptides and amino acid derivatives. Denise has experience with both solid and solution-phase peptide synthesis, and has worked under both research and cGMP settings. After completion of her MBA at Saint Joseph’s University, Denise transitioned into product management of peptides and amino acid derivatives. Denise has spent her time at PI focusing on both sales and marketing, including quoting, product management, market research and sales analysis, generating technical marketing content, and attending industry conferences.