It is well established that narrowed or blocked arteries can pose a serious threat to human health. Many medical procedures are available to treat such conditions, for example, balloon angioplasty and stenting, but patients often need to undergo further treatment due to failure of these therapies. Recently, a technology known as Natural Vascular Scaffolding<sup>TM</sup> (NVS) was developed to address these issues. Together with standard balloon angioplasty, the NVS procedure delivers a light-activatable naphthalimide-based small molecule, herein referred to as 10-8-10, to the vessel wall. Following penetration into and through the vessel wall, 10-8-10 is activated by illumination with a blue light fiber during angioplasty. This process serves to crosslink the native extracellular matrix proteins in the vessel wall creating a natural scaffolding effect. The proposed chemical mechanism of NVS involves crosslinking of readily oxidized amino acid side chains. We hypothesize that such reactions are initiated following single electron transfer (SET) events as mediated by 10-8-10. However, little is known regarding the particular amino acid residues that can undergo oxidation using these conditions. Considerable literature precedent guided early investigations focused on the photosensitized oxidation of tyrosine (Tyr) residues. This poster presentation will provide an overview of recent progress concerning the formation of dityrosine crosslinks (Tyr–Tyr) via 10-8-10-sensitized photooxidation of Tyr residues, as well as internal Tyr residues in peptides and proteins. Characterization efforts, including LC-MS, 1-D NMR, and 2-D NMR experiments, will be discussed.

Photosensitized tyrosine dimerization

ACS Fall 2020 Virtual Meeting

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