Publications de Christian Heinis

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Background In factor XI (FXI) deficiency, bleeding cannot be predicted by routine analyses. Since FXI is involved in tissue factor (TF)-independent propagation loop of coagulation, we hypothesized that investigating the spatiotemporal separated phases of c ...

Affinity selections by phage display or other display techniques are typically performed against single targets immobilized as a purified protein. In order to develop cross-specific binders that engage with multiple proteins, such as members of a related f ...

Photoswitchable ligands are powerful tools to control biological processes at high spatial and temporal resolution. Unfortunately, such ligands exist only for a limited number of proteins and their development by rational design is not trivial. We have dev ...

Fusion proteins of human O6-alkylguanine-DNA alkyltransferase (AGT) can be specifically labeled with a wide variety of synthetic probes in mammalian cells; this makes them an attractive tool for studying protein function. However, to avoid undesired labeli ...

We report the discovery of a small phenyl molecule with four isosteric thiolate-reactive groups of sequentially varied reactivity. This molecule was exploited in combination with cysteine/penicillamine thiolates of different nucleophilic reactivity for pre ...

The synthesis of large numbers of cyclic peptides-required, for example, in screens for drug development-is currently limited by the need of chromatographic purification of individual peptides. Herein, we have developed a strategy in which cyclic peptides ...

Cyclic peptides can bind challenging disease targets, but their oral application is hindered by digestion and absorption issues. We developed a versatile method for the synthesis and functional screening of vast numbers of synthetic cyclic peptides and ide ...

Macrocyclic compounds are an attractive class of therapeutic ligands against challenging targets, such as protein-protein interactions. However, the development of macrocycles as drugs is hindered by the lack of large combinatorial macrocyclic libraries, w ...

Macrocycles provide an attractive modality for drug development, but generating ligands for new targets is hampered by the limited availability of large macrocycle libraries. We have established a solution-phase macrocycle synthesis strategy in which three ...

A review. New, improved phenotypes. Somatic hypermutation in immune cells can be used for the fast directed evolution of proteins other than Igs (e.g., autofluorescent proteins). The target gene is inserted into the genome of activated B lymphocytes where ...

Phage display is a powerful technique routinely used for the generation of peptide- or protein-based ligands. The success of phage display selections critically depends on the size and structural diversity of the libraries, but the generation of large libr ...

DNA-encoded chemical library technologies enable the screening of large combinatorial libraries of chemically and structurally diverse molecules, including short cyclic peptides. A challenge in the combinatorial synthesis of cyclic peptides is the final st ...

Phage display relies on a bacterial infection step in which the phage particles are replicated to perform multiple affinity selection rounds and to enable the identification of isolated clones by DNA sequencing. While this process is efficient for wild-typ ...

Actin is the most abundant protein in eukaryotic cells and is key to many cellular functions. The filamentous form of actin (F-actin) can be studied with help of natural products that specifically recognize it, as for example fluorophore-labeled probes of ...

Combinatorial cyclization of hundreds to thousands of random linear peptides by structurally diverse chemical linkers offers access to large macrocyclic compound libraries. A bottleneck in the development of such libraries is the preparation of large numbe ...

Owing to their excellent binding properties, high stability, and low off-target toxicity, polycyclic peptides are an attractive molecule format for the development of therapeutics. Currently, only a handful of polycyclic peptides are used in the clinic; ex ...

Bicyclic peptides are small, constrained peptides that can bind with high affinity and selectivity to protein targets. Their small size provides a number of advantages over larger protein-based ligands, including access to chemical synthesis, better tissue ...

The invention regards a method for screening for interactions between two compounds provided in libraries. The invention in particular provides a method for screening interactions, such as a binding between two molecules or macromolecules, that is not limi ...

Coagulation factor XI (FXI) has emerged as a promising target for the development of safer anticoagulation drugs that limit the risk of severe and life-threatening bleeding. Herein, we report the first cyclic peptide-based FXI inhibitor that selectively an ...

Christian Heinis

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Tissue Factor-Independent Coagulation Correlates with Clinical Phenotype in Factor XI Deficiency and Replacement Therapy

Phage Display Selection against a Mixture of Protein Targets

Phage Selection of Photoswitchable Peptide Ligands

Engineering substrate specificity of O6-alkylguanine-DNA alkyltransferase for specific protein labeling in living cells

Precisely Regulated and Efficient Locking of Linear Peptides into Stable Multicyclic Topologies through a One-Pot Reaction

Cyclative Release Strategy to Obtain Pure Cyclic Peptides Directly from the Solid Phase

Development of cyclic peptides that can be administered orally to inhibit disease targets

Picomole-Scale Synthesis and Screening of Macrocyclic Compound Libraries by Acoustic Liquid Transfer

Macrocycle synthesis strategy based on step-wise “adding and reacting” three components enables screening of large combinatorial libraries

Fast directed evolution of non-immunoglobulin proteins by somatic hypermutation in immune cells

Generation of a 100-billion cyclic peptide phage display library having a high skeletal diversity

Synthesis of DNA‐encoded disulfide‐ and thioether‐cyclized peptides

Bypassing bacterial infection in phage display by sequencing DNA released from phage particles

In Vitro-Evolved Peptides Bind Monomeric Actin and Mimic Actin-Binding Protein Thymosin-β4

A releasable disulfide-linked peptide tag facilitates the synthesis and purification of short peptides

Polycyclic Peptide Therapeutics

Phage selection of bicyclic peptides

Phage display selection of peptides against the inflammation marker calprotectin and their application in a diagnostic assay

High complexity microcompartment-based interaction screening

Development of Selective FXIa Inhibitors Based on Cyclic Peptides and Their Application for Safe Anticoagulation