Dr. Martin Schnermann

Dr. Martin Schnermann
Organic Synthesis
301-228-4008

Research Summary

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. The limitations of existing methodologies dictate that researchers must choose from a small collection of probes whose chemical and physical properties are not ideal. We create reactions that enable the efficient preparation of novel near-IR fluorophores. We then use this chemistry to develop molecules with excellent chemical and photochemical stability and improved optical properties. These molecules are then applied towards several key cancer-related imaging 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.

Scientific Focus Areas:
Cancer Biology, Chemical Biology, Molecular Pharmacology

Positions Available. Contact Dr. Schnermann (martin.schnermann@nih.gov) with CV and cover letter.

PublicationsPatents

1 - 5 of 32 results

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1) Anderson Erin D, Sova Stacey, Ivanic Joseph, Kelly Lisa, Schnermann Martin J.
Defining the conditional basis of silicon phthalocyanine near-IR ligand exchange.
Phys Chem Chem Phys. 20: 19030-19036, 2018. [Journal]

2) Cha Jaepyeong, Nani Roger R, Luciano Michael P, Kline Gabriel, Broch Aline, Kim Kihoon, Namgoong Jung-Man, Kulkarni Rhushikesh A, Meier Jordan L, Kim Peter, Schnermann Martin J.
A chemically stable fluorescent marker of the ureter.
Bioorg. Med. Chem. Lett. 28: 2741-2745, 2018. [Journal]

3) Meier Jordan L, Schnermann Martin J.
Pharmacology by Chemical Biology.
Mol. Pharm. 15: 703-704, 2018. [Journal]

4) Gorka Alexander P, Yamamoto Tsuyoshi, Zhu Jianjian, Schnermann Martin J.
Cyanine Photocages Enable Spatial Control of Inducible Cre-Mediated Recombination.
Chembiochem. 19: 1239-1243, 2018. [Journal]

5) Nagaya Tadanobu, Gorka Alexander P, Nani Roger R, Okuyama Shuhei, Ogata Fusa, Maruoka Yasuhiro, Choyke Peter L, Schnermann Martin J, Kobayashi Hisataka.
Molecularly Targeted Cancer Combination Therapy with Near-Infrared Photoimmunotherapy and Near-Infrared Photorelease with Duocarmycin-Antibody Conjugate.
Mol. Cancer Ther. 17: 661-670, 2018. [Journal]

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