# Philipp E. Schilling > I develop amide-forming KAT ligation and organoboron protecting groups that make chemical protein synthesis possible at micromolar concentrations. I am a synthetic chemist working on chemical protein synthesis, chemoselective ligation, and organoboron chemistry. I did my Ph.D. with Jeffrey W. Bode at ETH Zurich, where I developed ONNO, a tetradentate ligand that masks potassium acyltrifluoroborates (KATs) as zwitterionic organoboron complexes so they survive Fmoc solid-phase peptide synthesis. With that masking strategy we were able to join peptide segments by KAT ligation at 100 to 200 micromolar - with roughly 50% conversion even at 20 micromolar, far below the millimolar concentrations that native chemical ligation and KAHA ligation require - and we used it to make human apolipoprotein C-I and the aggregation-prone immunoglobulin V domain of human PD-L2 (Science, 2026). I also helped develop a copper-catalyzed route from carboxylic acids to KATs (Angewandte Chemie, 2022). I am now a postdoctoral researcher in the Department of Pathology at Stanford University. Canonical name: Philipp E. Schilling. Also published as: P. E. Schilling, Philipp Schilling, P. Schilling, PE Schilling. ORCID: https://orcid.org/0000-0003-4996-5367 ## Publications - [Zwitterionic organoboron complexes for overcoming the concentration barrier in chemical protein synthesis](https://schillingp.com/publications/zwitterionic-organoboron-complexes-protein-synthesis-science-2026/): Science 2026, doi:10.1126/science.aea7511. This is the paper I am proudest of from my PhD. Chemical protein synthesis builds proteins by chemoselectively joining unprotected peptide segments, but the leading ligations - native chemical ligation and the alpha-ketoacid-hydroxylamine (KAHA) ligation - need millimolar concentrations, which fails for large, hydrophobic, or aggregation-prone segments that will not dissolve that concentrated. KAT ligation between potassium acyltrifluoroborates (KATs) and hydroxylamines stays fast even in dilute solution, but it had never worked for protein synthesis because no protecting group could carry a KAT through Fmoc solid-phase peptide synthesis. We solved this with ONNO, a tetradentate ligand that masks a KAT as a bench-stable, SPPS- and acid-stable zwitterionic organoboron complex and comes off again under mild conditions - which let us ligate peptide segments at micromolar concentrations. - [DMB labelling for detection and analysis of capsular polysaccharides](https://schillingp.com/publications/dmb-labelling-capsular-polysaccharides-biorxiv-2025/): bioRxiv 2025, doi:10.1101/2025.01.29.635457. A collaboration I contributed to while at ETH. Bacterial capsules are major virulence factors and vaccine antigens, but routine methods to detect and analyze them had largely disappeared. This study reports a biochemical method that releases ABC transporter-dependent (group 2 and 3) capsular polysaccharides by mild acid hydrolysis of their Kdo linkages and tags them fluorescently with DMB (1,2-diamino-4,5-methylenedioxybenzene); anion-exchange chromatography of the labelled material then reveals the presence, relative abundance, and length distribution of these antigens in extraintestinal pathogenic Escherichia coli (ExPEC). My contribution was insight into the DMB labelling chemistry. - [Potassium Acyltrifluoroborates (KATs) for Chemical Protein Synthesis and Modifications](https://schillingp.com/publications/kats-for-chemical-protein-synthesis-phd-thesis-eth-2025/): ETH Zurich 2025, doi:. My doctoral thesis, completed at ETH Zurich in the group of Jeffrey W. Bode. It covers my work on using potassium acyltrifluoroborates for chemical protein synthesis and protein modification, including the organoboron protecting-group strategies I developed to enable KAT ligation of peptide segments at low concentration. - [Heterobifunctional Linker](https://schillingp.com/publications/heterobifunctional-linker-patent-2025/): European Patent Application 2025, doi:. A European patent application for a heterobifunctional linker for bioconjugation, which I co-invented with colleagues at ETH Zurich. - [Preparation of Potassium Acyltrifluoroborates (KATs) from Carboxylic Acids by Copper-Catalyzed Borylation of Mixed Anhydrides](https://schillingp.com/publications/potassium-acyltrifluoroborates-from-carboxylic-acids-angewandte-2021/): Angew. Chem. Int. Ed. 2021, doi:10.1002/anie.202114513. Potassium acyltrifluoroborates (KATs) are the acylboron partners in KAT ligation, but before this work the only route from a carboxylic acid relied on a hard-to-handle borylzinc reagent. In this collaboration with the Mankad group we make KATs directly from carboxylic acids: we activate the acid as an isobutyl mixed anhydride with isobutyl chloroformate and N-methylmorpholine, borylate it with bis(pinacolato)diboron under a commercial N-heterocyclic-carbene copper catalyst (IMesCuCl) with sodium methoxide, and convert the product to the KAT with aqueous potassium bifluoride (KHF2). - [Mannosylated hemagglutinin peptides bind cyanovirin-N independent of disulfide-bonds in complementary binding sites](https://schillingp.com/publications/mannosylated-hemagglutinin-peptides-cyanovirin-n-rsc-advances-2020/): RSC Adv. 2020, doi:10.1039/d0ra01128b. This was my first paper, from my time in Vienna. Cyanovirin-N (CV-N) is an antiviral lectin that binds high-mannose glycans on enveloped viruses. I synthesized influenza hemagglutinin-derived peptides carrying mannose units through triazole linkers and measured how they bind CV-N variants with reduced disulfide content, including a variant in which one disulfide was replaced by an engineered glutamate/arginine ion pair. - [Studies of the binding of glycosylated peptides and influenza glycoproteins to recombinantly expressed Cyanovirin-N](https://schillingp.com/publications/glycosylated-peptides-cyanovirin-n-msc-thesis-vienna-2018/): University of Vienna 2018, doi:. My master's thesis at the University of Vienna, on synthesizing glycosylated peptides and measuring how influenza glycoproteins bind recombinant cyanovirin-N. This work became the basis of my 2020 RSC Advances paper on mannosylated hemagglutinin peptides and cyanovirin-N. ## Topics - [KAT ligation](https://schillingp.com/research/kat-ligation/): An overview of KAT ligation, the chemoselective amide-forming reaction between potassium acyltrifluoroborates and hydroxylamines, and its use in chemical protein synthesis and bioconjugation. ## Optional - [All references as BibTeX](https://schillingp.com/publications.bib) - [Google Scholar profile](https://scholar.google.com/citations?user=jJv11PUAAAAJ)