Large Libraries of Structurally Diverse Macrocycles Suitable for Membrane Permeation

A. L. Nielsen; Z. Bognar; G. K. Mothukuri; A. S. L. Zarda; M. Schuttel et al. 

Angewandte Chemie-International Edition. 2024-05-24. DOI : 10.1002/anie.202400350.

Solid-phase peptide synthesis in 384-well plates

M. Schuttel; E. Will; G. Sangouard; A. S. L. Zarda; S. Habeshian et al. 

Journal Of Peptide Science. 2024-01-14. DOI : 10.1002/psc.3555.



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

M. L. Merz; C. Heinis 

Nature Chemical Biology. 2023-12-28. DOI : 10.1038/s41589-023-01505-0.

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

M. Schuettel; C. Heinis 

Chembiochem. 2023-12-04. Vol. 25, num. 3. DOI : 10.1002/cbic.202300592.

De novo development of small cyclic peptides that are orally bioavailable

M. L. Merz; S. Habeshian; B. Li; J-A. G. L. David; A. L. Nielsen et al. 

Nature Chemical Biology. 2023-12-28. DOI : 10.1038/s41589-023-01496-y.

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

X-Y. Liu; X. Ji; C. Heinis; J. Waser 

Angewandte Chemie-International Edition. 2023-07-07. Vol. 62, num. 33, p. e202306036. DOI : 10.1002/anie.202306036.

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

C. Diaz-Perlas; B. Ricken; L. Farrera-Soler; D. Guschin; F. Pojer et al. 

Nature Communications. 2023-05-17. Vol. 14, num. 1, p. 2774. DOI : 10.1038/s41467-023-38075-7.

Motifs for making tricycles

C. Heinis 

Nature Chemical Biology. 2023-05-08. DOI : 10.1038/s41589-023-01329-y.


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

Z. Bognar; G. K. Mothukuri; A. L. Nielsen; M. L. Merz; P. M. F. Panzar et al. 

Organic & Biomolecular Chemistry. 2022-07-09. Vol. 20, num. 29, p. 5699-5703. DOI : 10.1039/d2ob00910b.

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

P. Gonschorek; A. Zorzi; T. Maric; M. Le Jeune; M. Schuettel et al. 

Journal Of Medicinal Chemistry. 2022-06-02. Vol. 65, num. 14, p. 9735-9749. DOI : 10.1021/acs.jmedchem.2c00306.

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

S. Habeshian; M. L. Merz; G. Sangouard; G. K. Mothukuri; M. Schüttel et al. 

Nature Communications. 2022-07-02. Vol. 13, num. 1, p. 3823. DOI : 10.1038/s41467-022-31428-8.

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

S. Habeshian; G. A. Sable; M. Schuettel; M. L. Merz; C. Heinis 

Acs Chemical Biology. 2022-01-11. Vol. 17, num. 1, p. 181–186. DOI : 10.1021/acschembio.1c00843.



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

V. Carle; X-D. Kong; A. Comberlato; C. Edwards; C. Diaz-Perlas et al. 

Protein Engineering Design & Selection. 2021-08-02. Vol. 34, p. gzab018. DOI : 10.1093/protein/gzab018.

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

G. Sangouard; A. Zorzi; Y. Wu; E. Ehret; M. Schuettel et al. 

Angewandte Chemie-International Edition. 2021-08-25. Vol. 60, num. 40, p. 21702-21707. DOI : 10.1002/anie.202107815.

Chemical Biology and Drug Discovery Symposium at the LS2 Annual Meeting 2021

C. Heinis; A. Calvente 

Chimia. 2021-04-01. Vol. 75, num. 4, p. 342-342. DOI : 10.2533/chimia.2021.342.

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

R. J. Gübeli; D. Bertoldo; K. Shimada; C. B. Gerhold; V. Hurst et al. 

ACS Chemical Biology. 2021-05-21. Vol. 16, num. 5, p. 820-828. DOI : 10.1021/acschembio.0c00825.

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

V. Carle; Y. Wu; R. Mukherjee; X-D. Kong; C. Rogg et al. 

Journal Of Medicinal Chemistry. 2021-05-27. Vol. 64, num. 10, p. 6802-6813. DOI : 10.1021/acs.jmedchem.1c00056.

Combining biological and chemical diversity

C. Heinis 

Nature Chemistry. 2021-06-01. Vol. 13, num. 6, p. 512-513. DOI : 10.1038/s41557-021-00722-1.

Combination of polycarboxybetaine coating and factor XII inhibitor reduces clot formation while preserving normal tissue coagulation during extracorporeal life support

N. Naito; R. Ukita; J. Wilbs; K. Wu; X. Lin et al. 

Biomaterials. 2021-05-01. Vol. 272, p. 120778. DOI : 10.1016/j.biomaterials.2021.120778.

Cys-Cys and Cys-Lys Stapling of Unprotected Peptides Enabled by Hypervalent Iodine Reagents

J. Ceballos; E. Grinhagena; G. Sangouard; C. Heinis; J. Waser 

Angewandte Chemie-International Edition. 2021-01-15. Vol. 60, num. 16, p. 9022-9031. DOI : 10.1002/anie.202014511.



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

D. Bertaggia Calderara; M. G. Zermatten; A. Aliotta; A. P. Batista Mesquita Sauvage; V. Carle et al. 

Thrombosis And Haemostasis. 2020-09-13. Vol. 121, num. 02, p. 150-163. DOI : 10.1055/s-0040-1715899.

Generation of a Large Peptide Phage Display Library by Self-Ligation of Whole-Plasmid PCR Product

X-D. Kong; V. Carle; C. Díaz-Perlas; K. Butler; C. Heinis 

ACS Chemical Biology. 2020-10-30. Vol. 15, num. 11, p. 2907-2915. DOI : 10.1021/acschembio.0c00497.

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

G. K. Mothukuri; S. S. Kale; C. L. Stenbratt; A. Zorzi; J. Vesin et al. 

Chemical Science. 2020-06-26. Vol. 11, num. 30, p. 7858-7863. DOI : 10.1039/D0SC01944E.

Cyclic peptide FXII inhibitor provides safe anticoagulation in a thrombosis model and in artificial lungs

J. Wilbs; X-D. Kong; S. J. Middendorp; R. Prince; A. Cooke et al. 

Nature Communications. 2020-08-04. Vol. 11, num. 1, p. 3890. DOI : 10.1038/s41467-020-17648-w.

De novo development of proteolytically resistant therapeutic peptides for oral administration

X-D. Kong; J. Moriya; V. Carle; F. Pojer; L. A. Abriata et al. 

Nature Biomedical Engineering. 2020-05-11. Vol. 4, p. 560–571. DOI : 10.1038/s41551-020-0556-3.

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

Y. Wu; A. Zorzi; J. Williams; C. Heinis 

Chemical Communications. 2020-03-07. Vol. 56, num. 19, p. 2917-2920. DOI : 10.1039/c9cc09247a.

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

M. V. Pham; M. Bergeron‐Brlek; C. Heinis 

ChemBioChem. 2020. Vol. 21, num. 4, p. 543-549. DOI : 10.1002/cbic.201900390.



Thiol-to-amine cyclization reaction enables screening of large libraries of macrocyclic compounds and the generation of sub-kilodalton ligands

S. S. Kale; M. Bergeron-Brlek; Y. Wu; M. G. Kumar; M. V. Pham et al. 

Science Advances. 2019-08-21. Vol. 5, num. 8, p. eaaw2851. DOI : 10.1126/sciadv.aaw2851.

Engineered peptide macrocycles can inhibit matrix metalloproteinases with high selectivity

K. Maola; J. Wilbs; J. Touati; M. Sabisz; X. Kong et al. 

Angewandte Chemie. 2019-06-28. Vol. 131, num. 34, p. 11927-11931. DOI : 10.1002/ange.201906791.



The Partnership of DMCCB and LS2

C. von Schoultz; C. Heinis; Y. Auberson 

Chimia. 2018-11-01. Vol. 72, num. 11, p. 817-818. DOI : 10.2533/chimia.2018.817.

Drugs Based on de novo-developed Peptides are Coming of Age

K. Deyle; C. Heinis 

Chimia. 2018-06-01. Vol. 72, num. 6, p. 426-427. DOI : 10.2533/chimia.2018.426.

Cyclization of peptides with two chemical bridges affords large scaffold diversities

S. Kale; C. Villequey; X. Kong; A. Zorzi; K. Deyle et al. 

Nature Chemistry. 2018. Vol. 10, num. 7, p. 715-723. DOI : 10.1038/s41557-018-0042-7.


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

C. Villequey; X-D. Kong; C. Heinis 

Protein Engineering, Design and Selection. 2017-11-29. Vol. 30, num. 11, p. 761-768. DOI : 10.1093/protein/gzx057.

Acylated heptapeptide binds albumin with high affinity and application as tag furnishes long-acting peptides

A. Zorzi; S. J. Middendorp; J. Wilbs; K. Deyle; C. Heinis 

Nature Communications. 2017. Vol. 8, p. 16092. DOI : 10.1038/ncomms16092.

Polar Hinges as Functionalized Conformational Constraints in (Bi) cyclic Peptides

H. Van De Langemheen; V. Korotkovs; J. Bijl; C. Wilson; S. S. Kale et al. 

Chembiochem. 2017. Vol. 18, num. 4, p. 387-395. DOI : 10.1002/cbic.201600612.

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

W. Liu; Y. Zheng; X. Kong; C. Heinis; Y. Zhao et al. 

Angewandte Chemie-International Edition. 2017. Vol. 56, num. 16, p. 4458-4463. DOI : 10.1002/anie.201610942.

Peptide macrocycle inhibitor of coagulation factor XII with subnanomolar affinity and high target selectivity

S. J. Middendorp; J. Wilbs; C. Quarroz; S. Calzavarini; A. Angelillo-Scherrer et al. 

Journal Of Medicinal Chemistry. 2017. Vol. 60, num. 3, p. 1151-1158. DOI : 10.1021/acs.jmedchem.6b01548.



Improving the binding affinity of in-vitro-evolved cyclic peptides by inserting atoms into the macrocycle backbone

J. Wilbs; S. J. Middendorp; C. Heinis 

Chembiochem. 2016. Vol. 17, num. 24, p. 2299-2303. DOI : 10.1002/cbic.201600336.

Phage selection of chemically stabilized alpha-helical peptide ligands

P. Diderich; D. Bertoldo; P. Dessen; M. M. Khan; I. Pizzitola et al. 

ACS Chemical Biology. 2016. Vol. 11, num. 5, p. 1422-1427. DOI : 10.1021/acschembio.5b00963.

Development of potent and selective S. aureus sortase A inhibitors Based on Peptide Macrocycles

I. R. Rebollo; S. Mccallin; D. Bertoldo; J. M. Entenza; P. Moreillon et al. 

ACS Medicinal Chemistry Letters. 2016. Vol. 7, num. 6, p. 606-611. DOI : 10.1021/acsmedchemlett.6b00045.

Phage selection of peptide macrocycles against b-catenin to interfere with Wnt signaling

D. Bertoldo; M. M. G. Khan; P. Dessen; W. Held; J. Huelsken et al. 

ChemMedChem. 2016. Vol. 11, num. 8, p. 834-839. DOI : 10.1002/cmdc.201500557.


Phage Selection of Bicyclic Peptide Ligands of the Notch1 Receptor

C. Urech-Varenne; F. Radtke; C. Heinis 

Chemmedchem. 2015. Vol. 10, num. 10, p. 1754-1761. DOI : 10.1002/cmdc.201500261.

A Synthetic Factor XIIa Inhibitor Blocks Selectively Intrinsic Coagulation Initiation

V. Baeriswyl; S. Calzavarini; S. Chen; A. Zorzi; L. Bologna et al. 

Acs Chemical Biology. 2015. Vol. 10, num. 8, p. 1861-1870. DOI : 10.1021/acschembio.5b00103.

Bicyclic Peptides Conjugated to an Albumin-Binding Tag Diffuse Efficiently into Solid Tumors

L. Pollaro; S. Raghunathan; J. Morales-Sanfrutos; A. Angelini; S. Kontos et al. 

Molecular Cancer Therapeutics. 2015. Vol. 14, num. 1, p. 151-161. DOI : 10.1158/1535-7163.Mct-14-0534.



Identification of target-binding peptide motifs by high-throughput sequencing of phage-selected peptides

I. R. Rebollo; M. Sabisz; V. Baeriswyl; C. Heinis 

Nucleic Acids Research. 2014. Vol. 42, num. 22, p. e169. DOI : 10.1093/nar/gku940.

Chemical biology & drug discovery

L. H. Jones; C. Heinis 

European Journal Of Medicinal Chemistry. 2014. Vol. 88, p. 1-2. DOI : 10.1016/j.ejmech.2014.10.017.

Phage selection of bicyclic peptides binding Her2

P. Diderich; C. Heinis 

Tetrahedron. 2014. Vol. 70, num. 42, p. 7733-7739. DOI : 10.1016/j.tet.2014.05.106.

Drug discovery: tools and rules for macrocycles

C. Heinis 

Nature chemical biology. 2014. Vol. 10, num. 9, p. 696-8. DOI : 10.1038/nchembio.1605.

Phage Selection of Photoswitchable Peptide Ligands

S. Bellotto; S. Chen; I. R. Rebollo; H. A. Wegner; C. Heinis 

Journal Of The American Chemical Society. 2014. Vol. 136, num. 16, p. 5880-5883. DOI : 10.1021/ja501861m.

Dithiol amino acids can structurally shape and enhance the ligand-binding properties of polypeptides

S. Chen; R. Gopalakrishnan; T. Schaer; F. Marger; R. Hovius et al. 

Nature Chemistry. 2014. Vol. 6, p. 1009-1016. DOI : 10.1038/nchem.2043.

Peptide ligands stabilized by small molecules

S. Chen; D. Bertoldo; A. Angelini; F. Pojer; C. Heinis 

Angewandte Chemie (International ed. in English). 2014. Vol. 53, num. 6, p. 1602-6. DOI : 10.1002/anie.201309459.


Tracking chemical reactions on the surface of filamentous phage using mass spectrometry

S. Chen; J. Touati; C. Heinis 

Chemical communications (Cambridge, England). 2013. Vol. 50, num. 40, p. 5267-5269. DOI : 10.1039/c3cc47496h.

Directed Evolution of Bicyclic Peptides for Therapeutic Application

P. Diderich; C. Heinis 

Chimia. 2013. Vol. 67, num. 12, p. 910-915. DOI : 10.2533/chimia.2013.910.

Improving binding affinity and stability of peptide ligands by substituting glycines with D-amino acids

S. Chen; D. Gfeller; S. A. Buth; O. Michielin; P. G. Leiman et al. 

Chembiochem : a European journal of chemical biology. 2013. Vol. 14, num. 11, p. 1316-1322. DOI : 10.1002/cbic.201300228.

Development of a selective peptide macrocycle inhibitor of coagulation factor XII toward the generation of a safe antithrombotic therapy

V. Baeriswyl; S. Calzavarini; C. Gerschheimer; P. Diderich; A. Angelillo-Scherrer et al. 

Journal of medicinal chemistry. 2013. Vol. 56, num. 9, p. 3742-3746. DOI : 10.1021/jm400236j.

Pattern-Based Sensing of Peptides and Aminoglycosides with a Single Molecular Probe

B. R. Lee; S. Chen; C. Heinis; R. Scopelliti; K. Severin 

Organic Letters. 2013. Vol. 15, p. 3456-3459. DOI : 10.1021/ol401495c.

Bicyclic peptide ligands pulled out of cysteine-rich peptide libraries

S. Chen; R. R. Inmaculada; S. A. Buth; J. Morales-Sanfrutos; J. Touati et al. 

Journal of the American Chemical Society. 2013. Vol. 135, num. 17, p. 6562-6569. DOI : 10.1021/ja400461h.

Phage display libraries of differently sized bicyclic peptides

I. R. Rebollo; A. Angelini; C. Heinis 

Medchemcomm. 2013. Vol. 4, num. 1, p. 145-150. DOI : 10.1039/c2md20171b.

Polycyclic Peptide Therapeutics

V. Baeriswyl; C. Heinis 

Chemmedchem. 2013. Vol. 8, num. 3, p. 377-384. DOI : 10.1002/cmdc.201200513.

Phage selection of cyclic peptide antagonists with increased stability toward intestinal proteases

V. Baeriswyl; C. Heinis 

Protein engineering, design & selection : PEDS. 2013. Vol. 26, num. 1, p. 81-89. DOI : 10.1093/protein/gzs085.