Martin J. Schnermann, Ph.D.

Investigator

Chemical Biology Laboratory

NCI/CCR

Building 376, Room 225D
Frederick, MD 21702

301-228-4008

schnermannmj@mail.nih.gov

Research Topics

Near-IR Uncaging Chemistry: Discovery and Applications

Many key fundamental and applied questions in biology require unraveling issues relating to the spatial and temporal organization of multi-cellular systems. The combination of photocaged small molecule probes and the spatially controlled application of light could, in principle, provide key insights. However, existing photoremovable caging groups are often not suitable, particularly for organismal applications. This is due to the general requirement of UV or blue light, which suffers from associated toxicity and poor tissue penetration. By contrast, light between 650 and 900 nm, often referred to as the near-IR window, is cytocompatible and has significant tissue penetration. My group develops new single photon near-IR uncaging methods. The modest photonic energy of these wavelengths makes this a challenging chemistry problem. Our approach is to define and then take advantage of photochemical reactions of long-wavelength fluorophores. In our most advanced project, we have shown that the photooxidative reactivity of heptamethine cyanines can be used for small molecule drug delivery. Using these molecules, we are developing a general strategy for highly targeted in vivo drug delivery using antibody targeting. In a separate approach, we have also shown that the photoredox ligand exchange of silicon phthalocyanines can be used for hypoxia-selective near-IR uncaging.

Modern Synthetic Approaches for Small Molecule Imaging

There is a significant need for improved near-IR fluorophores for emerging applications in basic and applied biomedical science. Existing molecules are often prepared through inefficient classical synthetic methods that suffer from poor substrate scope and harsh reaction conditions. We create reactions that enable the efficient preparation of novel near-IR fluorophores. This new chemistry is used to develop molecules with improved stability and optical properties. We are particularly focused on developing compounds suitable for fluorescence-guided surgery applications. In related efforts, we are mining the structural diversity of natural products for light emitting scaffolds to develop broadly useful optical probes. Key to this work is the development of concise total syntheses to access compounds of interest. 

Biography

Dr. Schnermann attended Colby College and graduated in 2002 with degrees in Chemistry and Physics. At Colby, he worked with Prof. Dasan Thamattoor in the areas of physical organic chemistry and photochemistry. After a year at Pfizer Research and Development (Groton, CT) as an associate in the medicinal chemistry division, he moved to the Scripps Research Institute. During his graduate studies, he performed research on the total synthesis and biological evaluation of anticancer natural products with Prof. Dale Boger and obtained a Ph.D. in 2008. He then completed an NIH-postdoctoral fellowship with Prof. Larry Overman at the University of California, Irvine. At Irvine, he developed light-mediated reactions to enable the synthesis of complex natural products. In addition, working with Prof. Christine Suetterlin, he pursued chemical biology and imaging studies of organelle specific probes. In 2012, Dr. Schnermann joined the NCI where his research focuses on the synthesis and development of new small-molecule imaging agents for cancer treatment and diagnosis.   

Selected Publications

  1. Nani RR, Gorka AP, Nagaya T, Yamamoto T, Ivanic J, Kobayashi H, Schnermann MJ. <i>In Vivo</i> Activation of Duocarmycin-Antibody Conjugates by Near-Infrared Light. ACS Cent Sci. 2017;3(4):329-337.

  2. Nani RR, Shaum JB, Gorka AP, Schnermann MJ. Electrophile-integrating Smiles rearrangement provides previously inaccessible C4'-O-alkyl heptamethine cyanine fluorophores. Org Lett. 2015;17(2):302-5.

  3. Nani RR, Gorka AP, Nagaya T, Kobayashi H, Schnermann MJ. Near-IR Light-Mediated Cleavage of Antibody-Drug Conjugates Using Cyanine Photocages. Angew Chem Int Ed Engl. 2015;54(46):13635-8.

  4. Nani RR, Kelley JA, Ivanic J, Schnermann MJ. Reactive Species Involved in the Regioselective Photooxidation of Heptamethine Cyanines. Chem Sci. 2015;6(11):6556-6563.

  5. Gorka AP, Nani RR, Zhu J, Mackem S, Schnermann MJ. A near-IR uncaging strategy based on cyanine photochemistry. J Am Chem Soc. 2014;136(40):14153-9.


This page was last updated on July 11th, 2017