Publications by Christian Heinis

Structure‐affinity relationship analysis and affinity maturation of a calprotectin‐binding peptide

Christian Heinis, Lluc Farrera Soler, Cristina Diaz Perlas

Peptide 3 is an 18‐amino acid linear peptide binding with sub‐micromolar affinity to the inflammation marker calprotectin. Its application in point‐of‐care diagnostic assays has shown promising results, yet improving its affinity for calprotectin could fac ...

Wiley2025

Bulk measurement of membrane permeability for random cyclic peptides in living cells to guide drug development

Christian Heinis, Alexander Lund Nielsen, Anne Sofie Luise Zarda

Cyclic peptides are attractive for drug discovery due to their excellent binding properties and the potential to cross cell membranes. However, by far not all cyclic peptides are cell permeable, and measuring or predicting their membrane permeability is no ...

Wiley2025

Phage Display Selection against a Mixture of Protein Targets

Christian Heinis, Xudong Kong

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 ...

American Chemical Society (ACS)2025

Biodiversity2Drugs—Renaissance of exploring nature‐derived peptides for GPCR ligand discovery

Christian Heinis

Wiley2025

Discovery of De Novo Macrocycle Inhibitors of Histone Deacetylase 11

Christian Heinis, Edward Jeffrey Will, Alexander Lund Nielsen, Anne Sofie Luise Zarda

Histone deacetylase (HDAC) enzymes are epigenetic regulators that affect diverse protein function by removing acyl groups from lysine side chains throughout the proteome. The most recently discovered human isozyme, HDAC11, differs from other HDACs in subst ...

2025

Screening macrocyclic peptide libraries by yeast display allows control of selection process and affinity ranking

Christian Heinis, Lluc Farrera Soler, Edward Jeffrey Will

Springer Science and Business Media LLC2025

Solid-phase peptide synthesis in 384-well plates

Christian Heinis, Gontran Sangouard, Mischa Schüttel, Sevan Mleh Habeshian, Edward Jeffrey Will, Alexander Lund Nielsen, Anne Sofie Luise Zarda

Newer solid-phase peptide synthesis and release strategies enable the production of short peptides with high purity, allowing direct screening for desired bioactivity without prior chromatographic purification. However, the maximum number of peptides that ...

2024

Cyclic Peptides for Drug Development

Christian Heinis, Xinjian Ji, Alexander Lund Nielsen

Cyclic peptides are fascinating molecules abundantly found in nature and exploited as molecular format for drug development as well as other applications, ranging from research tools to food additives. Advances in peptide technologies made over many years ...

Wiley-VCH Verlag GmbH2024

Large Libraries of Structurally Diverse Macrocycles Suitable for Membrane Permeation

Christian Heinis, Alessandro Angelini, Mischa Schüttel, Ganesh Kumar Mothukuri, Manuel Leonardo Merz, Zsolt Bognár, Xinjian Ji, Edward Jeffrey Will, Alexander Lund Nielsen, Anne Sofie Luise Zarda

Macrocycles offer an attractive format for drug development due to their good binding properties and potential to cross cell membranes. To efficiently identify macrocyclic ligands for new targets, methods for the synthesis and screening of large combinator ...

Wiley-VCH Verlag GmbH2024

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

Christian Heinis, Jérôme Waser, Xinjian Ji, Xingyu Liu

Swiss Chemical Soc2023

De novo development of small cyclic peptides that are orally bioavailable

Christian Heinis, Manuel Leonardo Merz, Sevan Mleh Habeshian, Xinjian Ji, Alexander Lund Nielsen, Bo Li

Cyclic peptides can bind challenging disease targets with high affinity and specificity, offering enormous opportunities for addressing unmet medical needs. However, as with biological drugs, most cyclic peptides cannot be applied orally because they are r ...

2023

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

Christian Heinis, Jérôme Waser, Xinjian Ji, Xingyu Liu

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 ...

Wiley-VCH Verlag GmbH2023

High-Density Immobilization of TCEP on Silica Beads for Efficient Disulfide Reduction and Thiol Alkylation in Peptides

Christian Heinis

Tris-(2-carboxyethyl)phosphine (TCEP) linked to agarose beads is widely used for reducing disulfide bridges in proteins and peptides. The immobilization of TCEP on beads allows efficient removal after reduction to prevent its reaction with alkylating reage ...

2023

High-affinity peptides developed against calprotectin and their application as synthetic ligands in diagnostic assays

Christian Heinis, Florence Pojer, Lluc Farrera Soler, Kelvin Ka Ching Lau, Cristina Diaz Perlas

A peptide was developed that binds to calprotectin, a marker of major inflammatory disorders, and found to be suited for diagnostic tests. The use of synthetic peptides in assays is of great interest due to their high precision, robustness and low price. ...

Nature Portfolio2023

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

Christian Heinis, Manuel Leonardo Merz

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 ...

2023

Synthesis and direct assay of large macrocycle diversities by combinatorial late-stage modification at picomole scale

Gerardo Turcatti, Jonathan Patrice Vesin, Christian Heinis, Alessandro Angelini, Gontran Sangouard, Julien Bortoli Chapalay, Mischa Schüttel, Ganesh Kumar Mothukuri, Manuel Leonardo Merz, Sevan Mleh Habeshian, Cristina Diaz Perlas, Zsolt Bognár

Macrocycles have excellent potential as therapeutics due to their ability to bind challenging targets. However, generating macrocycles against new targets is hindered by a lack of large macrocycle libraries for high-throughput screening. To overcome this, ...

Nature Research2022

Solid-phase peptide synthesis on disulfide-linker resin followed by reductive release affords pure thiol-functionalized peptides

Christian Heinis, Ganesh Kumar Mothukuri, Manuel Leonardo Merz, Zsolt Bognár, Peter Matei Frisius Pânzar, Alexander Lund Nielsen

Thiol groups are suitable handles for site-selectively modifying, immobilizing or cyclizing individual peptides or entire peptide libraries. A limiting step in producing the thiol-functionalized peptides is the chromatographic purification, which is partic ...

2022

High complexity microcompartment-based interaction screening

Christian Heinis

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 ...

2022

Phage Display Selected Cyclic Peptide Inhibitors of Kallikrein-Related Peptidases 5 and 7 and Their In Vivo Delivery to the Skin

Luc Reymond, Christian Heinis, Alessandro Zorzi, Mischa Schüttel, Vanessa Carle, Tamara Maric, Patrick Andreas Gonschorek

Kallikrein-related peptidases 5 (KLK5) and 7 (KLK7) are serine proteases with homeostatic functions in the epidermis that play a critical role in Netherton syndrome (NS), a rare yet life-threatening genetic disorder that currently lacks specific treatment. ...

AMER CHEMICAL SOC2022

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

Christian Heinis, Cristina Diaz Perlas

WILEY2022