Laboratory of Therapeutic Proteins and Peptides

Laboratory

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The phenomenon of allostery, a general property in proteins that has been heralded as "the second secret of life" remains elusive to our understanding and even more challenging to incorporate into protein design. One example of allosteric proteins with gre ...

As the fundamental machinery orchestrating cellular functions, proteins influence the state of every cell profoundly. As cells exhibit significant variations from one to another, analyzing the proteome on a single-cell level is imperative to unravel their ...

Proteins control nearly every facet of life on a molecular level. Proteins are formed from linear strings of amino acids, which fold into three-dimensional structures that can enact functions. Evolution has created highly efficient proteins in diverse fold ...

Protein-protein interactions (PPIs) are responsible for regulating many biological processes in human bodies. PPIs often have a large binding site and often interact through an alpha helical segment. Therefore, the inhibition of PPIs can be difficult using ...

Herein, we report a novel strategy for the modification of peptides based on the introduction of highly reactive hypervalent iodine reagents-ethynylbenziodoxolones (EBXs)-onto peptides. These peptide-EBXs can be readily accessed, by both solution- and soli ...

Macrocycles have raised much interest in the pharmaceutical industry due to their ability to bind challenging targets while often still being able to cross membranes to reach intracellular proteins. However, the development of macrocyclic ligands to new di ...

Cyclic peptides are ring-shaped molecules that emerged as a promising class of therapeutics. While it is often difficult to find small molecule binders for challenging disease targets, cyclic peptides can bind to featureless surfaces or inhibit protein-pro ...

Sirtuin 5 (SIRT5) is a protein lysine deacylase enzyme that regulates diverse biology by hydrolyzing epsilon-N-carboxyacyllysine posttranslational modifications in the cell. Inhibition of SIRT5 has been linked to potential treatment of several cancers but ...

The goal of my PhD was the development of a new method for unselective surface labeling, not substrate-specific, that would give access to direct visualization of any surface interactions. In order to achieve this challenging goal, we wanted to develop a g ...

Protein Engineering, especially protein post-translational modification (PTM), ex-tends proteomes in a more complex way than one can expect from analysis of their encod-ing genomes. It can activate or deactivate certain catalytic functions, add new desired ...

The sheer size of the protein sequence space is massive: a protein of 100 residues can have 20^100 possible sequence combinations; and knowing that this exceeds the number of atoms in the universe, the chance of randomly discovering a stable new sequence w ...

Recent advances in protein-design methodology have led to a dramatic increase in reliability and scale. With these advances, dozens and even thousands of designed proteins are automatically generated and screened. Nevertheless, the success rate, particular ...

Macrocycles are an attractive class of molecules due to their good binding properties and yet rather small size that allows, in many cases, crossing membranes to reach intracellular targets. In comparison to classical small molecule drugs, macrocycles are ...

Developing molecules that emulate the properties of naturally occurring ice-binding proteins (IBPs) is a daunting challenge. Rather than relying on the (limited) existing structure–property relationships that have been established for IBPs, here we report ...

Proteins are fundamental components in biological systems and crucial for a variety of biological functions. Over the last decades, significant progress in structural biology has facilitated the study of proteins and their interactions with molecular partn ...

Hypervalent iodine compounds are powerful reagents for the development of novel transformations. As they exhibit low toxicity, high functional group tolerance, and stability in biocompatible media, they have been used for the functionalization of biomolecu ...

A photoredox-catalyzed oxidative decarboxylative coupling of small peptides is reported, giving access to a variety of N,O-acetals. They were used as intermediates for the addition of phenols and indoles, leading to novel peptide scaffolds and bioconjugate ...

If small molecules have led to tremendous progress in curing diseases, new therapeutic agents such as peptides or antibody-drugs conjugates have emerged as a highly promising next generation of pharmaceuticals. As for small molecules, their derivatization ...

The oral administration of peptide drugs is hampered by their metabolic instability and limited intestinal uptake. Here, we describe a method for the generation of small target-specific peptides (less than 1,600 Da in size) that resist gastrointestinal pro ...

Designing compounds that bind to the acidic patch of the nucleosome core particle (NCP) is an emerging therapeutic approach that can inhibit the binding of key chromatin factors. Pretreatment of human ovarian carcinoma, A2780, cells with RAPTA-T, an antime ...

Laboratory of Therapeutic Proteins and Peptides

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From Sequence to Dynamics to Function: Computational Design of Allostery and Ligand Selectivity in G-Protein Coupled Receptors

Development of tools and methods for protein identification: From single molecules to in vivo applications

De novo designed proteins: a study in engineering novel folds and functions

Synthesis and application of bifunctional hypervalent iodine reagents for peptide modification

Peptide-Hypervalent Iodine Reagent Chimeras: Enabling Peptide Functionalization and Macrocyclization

Development of methods for the synthesis of large combinatorial libraries of macrocyclic compounds

De novo developed small cyclic peptides that are orally available

Investigation of Carboxylic Acid Isosteres and Prodrugs for Inhibition of the Human SIRT5 Lysine Deacylase Enzyme

Azide-Containing Hypervalent Iodine Reagents for Biomolecules Functionalization

Protein Engineering for Personalized therapy and diagnosis

Towards automating de novo protein design for novel functionalities: controlling protein folds and protein-protein interactions

Assessing and enhancing foldability in designed proteins

Methods for the generation of large combinatorial macrocycle libraries

A minimalistic cyclic ice-binding peptide from phage display

On the exploration of novel methodological approaches for immunogen design: case studies in influenza and hepatitis C

Hypervalent Iodine-Mediated Late-Stage Peptide and Protein Functionalization

Small peptide diversification through photoredox-catalyzed oxidative C-terminal modification

Development of Photocatalysts towards the Visible-Light driven C-Terminal Bioconjugation of Peptides and Proteins

De novo development of proteolytically resistant therapeutic peptides for oral administration

Crosslinking Allosteric Sites on the Nucleosome Core Particle