Philipp Schilling

All Publications

• Zwitterionic organoboron complexes for overcoming the concentration barrier in chemical protein synthesis SCIENCE Schilling, P. E., Steiner, S., Bode, J. W. 2026; 391 (6785): 598-603

  Abstract

  Chemical protein synthesis enables the construction of specific protein architectures but is limited to millimolar reaction concentrations, restricting access to poorly soluble proteins. Potassium acyltrifluoroboronates (KATs) offer a promising alternative through fast and chemoselective amide bond formation, but their application to protein synthesis has been precluded by the lack of a masking strategy. We report chiral, zwitterionic organoboron complexes that mask amino acid-derived KATs. These molecules exhibit unexpected nitrogen-carbon-boron connectivity and are fully compatible with solid-phase peptide synthesis and stereoretentive deprotection. We synthesized C-terminal KAT peptides and demonstrated KAT ligation at micromolar concentrations for the convergent synthesis of the aggregation-prone programmed death ligand 2 (PD-L2) immunoglobulin V domain. This work establishes organoboron chemistry as an enabling strategy for chemical protein synthesis at low concentrations far more suitable for handling large, aggregation-prone biomolecules.

  View details for DOI 10.1126/science.aea7511

  View details for Web of Science ID 001698264300012

  View details for PubMedID 41643010

• Preparation of Potassium Acyltrifluoroborates (KATs) from Carboxylic Acids by Copper-Catalyzed Borylation of Mixed Anhydrides** ANGEWANDTE CHEMIE-INTERNATIONAL EDITION Tung, P., Schuhmacher, A., Schilling, P. E., Bode, J. W., Mankad, N. P. 2022; 61 (7): e202114513

  Abstract

  We report the preparation of potassium acyltrifluoroborates (KATs) from widely available carboxylic acids. Mixed anhydrides of carboxylic acids were prepared using isobutyl chloroformate and transformed to the corresponding KATs using a commercial copper catalyst, B2 (pin)2 , and aqueous KHF2 . This method allows for the facile preparation of aliphatic, aromatic, and amino acid-derived KATs and is compatible with a variety of functional groups including alkenes, esters, halides, nitriles, and protected amines.

  View details for DOI 10.1002/anie.202114513

  View details for Web of Science ID 000736062000001

  View details for PubMedID 34913236

• Mannosylated hemagglutinin peptides bind cyanovirin-N independent of disulfide-bonds in complementary binding sites RSC ADVANCES Schilling, P. E., Kontaxis, G., Dragosits, M., Schiestl, R. H., Becker, C. F. W., Maier, I. 2020; 10 (19): 11079-11087

  Abstract

  Cyanovirin-N (CV-N) has been shown to reveal broad neutralizing activity against human immunodeficiency virus (HIV) and to specifically bind Manα(1→2)Manα units exposed on various glycoproteins of enveloped viruses, such as influenza hemagglutinin (HA) and Ebola glycoprotein. Chemically synthesized dimannosylated HA peptides bound domain-swapped and dimeric CV-N with either four disulfide-bonds (Cys-Cys), or three Cys-Cys bonds and an intact fold of the high-affinity binding site at an equilibrium dissociation constant K D of 10 μM. Cys-Cys mutagenesis with ion-pairing amino-acids glutamic acid and arginine was calculated by in silico structure-based protein design and allowed for recognizing dimannose and dimannosylated peptide binding to low-affinity binding sites (K D ≈ 11 μM for one C58-C73 bond, and binding to dimannosylated peptide). In comparison, binding to HA was achieved based on one ion-pairing C58E-C73R substitution at K D = 275 nM, and K D = 5 μM for two C58E-C73R substitutions. We were utilizing a triazole bioisostere linkage to form the respective mannosylated-derivative on the HA peptide sequence of residues glutamine, glycine, and glutamic acid. Thus, mono- and dimannosylated peptides with N-terminal cysteine facilitated site-specific interactions with HA peptides, mimicking a naturally found N-linked glycosylation site on the HA head domain.

  View details for DOI 10.1039/d0ra01128b

  View details for Web of Science ID 000523640500011

  View details for PubMedID 35495330

  View details for PubMedCentralID PMC9050506