Organic Seminar - Monika Raj

In the Raj Lab, we are focused on developing novel chemical probes and sensors aimed at targeting the undruggable proteome, along with enabling the selective detection of post-translational modifications (PTMs) and biological metabolites. Our research drives the discovery of new protein biomarkers, therapeutic targets, and affordable diagnostic tools for the early detection of cancer. By identifying endogenous protein partners, we also facilitate the synthesis of biotherapeutics. In the first part of my talk, I will highlight our efforts to develop advanced bioconjugation techniques for the selective labeling of key amino acids such as lysine, methionine, asparagine, and glutamine, as well as PTMs like mono-methyl lysine, di-methyl lysine, and monomethyl-histidine.^1-5 These new labeling strategies address current gaps in the techniques available for sequencing and identifying proteins and PTMs, enabling single-molecule and single-cell analysis with high sensitivity and accuracy. In the second part of the talk, I will discuss our work on Protein Restoration Technology (PRT), which aims to restore the function of mutated tumor suppressor proteins. This technology provides a novel therapeutic approach for targeting aberrant proteins, offering new opportunities to develop treatments for cancer and other diseases. Through PRT, we can revive the functions of tumor suppressors lost due to mutations, ultimately paving the way for new therapies that target undruggable proteins and restore normal cellular functions.

References and Notes:

1. Emenike, B.; Paikin, Z. E.; Talbott, J. M.; Lidskog, A.; Le, B. Q. G.; Swaminathan, J.; Anslyn, E. V.; Raj, M. Coarctate reaction for synthesis of fluorescent N-heterocycles, late-stage functionalization, and photo-triggered drug delivery. J. Am. Chem. Soc. 2026, DOI: 10.1021/jacs.5c22184
2. Sahu, S.; Paikin, Z. E.; Talbott, J. M.; Czabala^, P.; Raj, M. Coarctate reaction for synthesis of fluorescent N-heterocycles, late-stage functionalization, and photo-triggered drug delivery. Nat. Commun. 2025, 16, 3780.
3. Sahu, S.; Emenike, B.; Buesch, C. M.; Bagchi, P.; Gordon, D. E.; Raj, M. Copper(I)-nitrene platform for chemoproteomic profiling of methionine. Nat. Commun. 2024, 15, 4243
4. Emenike, B.; Czabala, P.; Farhi, J.; Swaminathan, J.; Anslyn, E. V.; Spangle, J.; Raj, M. Tertiary amine coupling by oxidation for selective labelling of dimethyl lysine post-translational modifications. J. Am. Chem. Soc. 2024, 146, 10621-10631.
5. Emenike, B.; Donovan, J.; Raj, M. Multicomponent oxidative nitrile thiazolidination reaction for selective modification of N-terminal dimethylation posttranslational modification. J. Am. Chem. Soc. 2023, 154, 16417-16428.