Bruno N. Melillo

Targeting proteasome composition reprograms tumor-intrinsic inflammation through selective degradation of STAT1

This study identifies a small molecule targeting PSME4, which stabilizes STAT1 and reprograms tumor inflammation, suppressing tumor growth by altering cytokine signaling.

Activity-based profiling of primary brain cells identifies covalent allosteric modulators of HCN channels

ESCAPE: assigning site-specific activity to covalent ligands in cells by prime editing

ESCAPE identifies covalent ligand-protein interactions by using prime editing to disrupt cysteine residues and assesses their impact on cellular phenotypes.

A Global Ligandability Map of Tryptoline Butynamide Stereoprobes Identifies Covalent Inhibitors of the Actin Maturation Protease ACTMAP

The paper compares acrylamide and butynamide stereoprobes to identify covalent inhibitors of the actin maturation protease ACTMAP in human cancer cells.

Minimum inoculum of resistance assay for evaluating for anti-toxoplasmosis compounds that target phenyl alanine tRNA synthetase

The paper develops a Minimum Inoculum for Resistance (MIR) assay to evaluate anti-Toxoplasma gondii compounds, showing that inhibitors of phenylalanine tRNA synthetase require higher parasite inocula to induce resistance compared to DNA synthesis inhibitors.

Mapping ortholog-restricted ligandable cysteines in the wheat pathogen Zymoseptoria tritici

The paper identifies ortholog-restricted cysteines in Z. tritici that are targeted by stereoprobes, revealing potential fungicidal targets for combating wheat pathogens.

High-throughput diversification of protein-ligand surfaces to discover chemical inducers of proximity

This study uses high-throughput chemistry to discover chemical inducers of proximity by modifying pre-existing ligands and screening for degrader activity.

Integrated phenotypic screening and chemical proteomics identifies ETF1 ligands that modulate viral translation and replication

Cysteine reactivity profiling identifies host regulators of Mycobacterium tuberculosis replication in human macrophages

The paper identifies host proteins regulating Mycobacterium tuberculosis replication in macrophages using cysteine reactivity profiling and genetic perturbation.

Structural and mechanistic analysis of covalent ligands targeting the RNA-binding protein NONO

This paper reports covalent ligands targeting the RNA-binding protein NONO, showing they stabilize mRNA interactions, remodel transcriptomes, and suppress cancer cell growth with high specificity.

Complexoform-restricted covalent TRMT112 ligands that allosterically agonize METTL5

The paper develops covalent ligands that specifically target a complexoform of TRMT112, revealing partner-specific functional effects through allosteric activation of METTL5.

Tryptoline Stereoprobe Elaboration Identifies Inhibitors of the GRPEL1-HSPA9 Chaperone Complex

The paper identifies inhibitors of the GRPEL1-HSPA9 chaperone complex using tryptoline stereoprobes and shows they target non-orthosteric sites.

A cold-inducible phospholipid--protein interaction in brown fat mitochondria optimizes thermogenic capacity

The paper identifies LPCAT3 as a cold-regulated enzyme that generates AA-PE in BAT mitochondria, enhancing ETC efficiency and thermogenesis.

Proteomic Ligandability Maps of Phosphorus(V) Stereoprobes Iden-tify Covalent TLCD1 Inhibitors

The paper uses stereoprobes to identify covalent ligands for proteins, revealing TLCD1 as a lipid acyltransferase inhibited by OTP stereoprobes.

Chemical tools to expand the ligandable proteome: diversity-oriented synthesis-based photoreactive stereoprobes

The paper introduces photo-stereoprobes for expanding the ligandable proteome and demonstrates their use in discovering bioactive small molecules.

Redirecting the pioneering function of FOXA1 with covalent small molecules

This study identifies covalent small molecules that bind FOXA1, altering its chromatin remodeling activity in prostate cancer cells.

Bicyclic pyrrolidine inhibitors of Toxoplasma gondii phenylalanine t-RNA synthetase with antiparasitic potency in vitro and brain exposure

This paper describes new bicyclic pyrrolidine inhibitors of Toxoplasma gondii PheRS with improved potency, selectivity, and brain exposure compared to previous azetidine-based inhibitors.

Assigning functionality to cysteines by base editing of cancer dependency genes

The paper uses base editing to assess the functional impact of cysteine mutations in cancer dependency genes, identifying essential and ligandable cysteines for drug development.