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Dr. Martin Schnermann


Dr. Martin Schnermann
Organic Synthesis
301-228-4008

Research Summary

Near-IR Light-Cleavable Linkers for Targeted Drug Delivery
Light is used in a variety of cancer treatments ranging from well-established therapeutic techniques, such as PDT, to emerging areas such as fluorescence-guided surgery. Separately, the last decade has seen the clinical success of a number of antibody-drug conjugates. An enduring challenge is the development of precisely controlled linker strategies. To address this, we are developing light-cleavable linkers for targeted drug delivery. This approach would merge the unique potency of small molecule drugs with the high spatial control afforded by light release and molecular targeting. Central to our efforts is the development of release or uncaging reactions initiated by tissue penetrant, cytocompatible near-IR light. This is critical because existing uncaging chemistry uses UV or blue light, which is not suitable for many in vivo applications. To develop near-IR uncaging reactions, we use the intrinsic chemistry of near-IR fluorophores. These reactions were often first encountered in the context of mechanistic studies to determine the basis of fluorophore photochemical decomposition or photobleaching. Using the inherent reactivity of near-IR fluorophores, we are developing broadly useful tools for targeted drug delivery, with additional applications in a variety of contexts where near-IR uncaging would be beneficial.
Fluorophores for Cancer Imaging
The discovery and implementation of molecularly targeted optical imaging modalities for cancer diagnosis and treatment has progressed considerably. The development of bright, chemically stable, and easily synthesized fluorophores in the near-IR range is critical for clinical advances in this area. Despite a central role in modern biology techniques, the compounds employed in near-IR fluorescence have changed little in recent decades. The studies discussed above have provided a number of insights regarding the reactivity of common near-IR fluorophore scaffolds. For example, we have encountered compounds with improved chemical stability and reduced photobleaching rates. Using these insights, and molecular design principles and techniques borrowed from related fields (e.g. medicinal chemistry and modern organic synthesis), we seek to develop improved variants of these extensively used biological tools.
PublicationsPatents
1 - 5 of 7 results

1)  Schnermann MJ, Overman LE.
A Concise Synthesis of (-)-Aplyviolene Facilitated by a Strategic Tertiary Radical Conjugate Addition.
Angew. Chem. Int. Ed. Engl. 2012. [Journal]

2)  Schnermann MJ, Untiedt NL, Jiménez-Osés G, Houk KN, Overman LE.
Forming Tertiary Organolithiums and Organocuprates from Nitrile Precursors and their Bimolecular Reactions with Carbon Electrophiles to Form Quaternary Carbon Stereocenters.
Angew. Chem. Int. Ed. Engl. 2012. [Journal]

3)  Schnermann MJ, Beaudry CM, Genung NE, Canham SM, Untiedt NL, Karanikolas BD, Sütterlin C, Overman LE.
Divergent synthesis and chemical reactivity of bicyclic lactone fragments of complex rearranged spongian diterpenes.
J. Am. Chem. Soc. 133: 17494-503, 2011. [Journal]

4)  Schnermann MJ, Overman LE.
Enantioselective total synthesis of aplyviolene.
J. Am. Chem. Soc. 133: 16425-7, 2011. [Journal]

5)  Schnermann MJ, Beaudry CM, Egorova AV, Polishchuk RS, Sütterlin C, Overman LE.
Golgi-modifying properties of macfarlandin E and the synthesis and evaluation of its 2,7-dioxabicyclo[3.2.1]octan-3-one core.
Proc. Natl. Acad. Sci. U.S.A. 107: 6158-63, 2010. [Journal]

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