Publications de Kaycie Marie Butler

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

Christian Heinis, Chloé Rogg, Xudong Kong, Vanessa Carle, Cristina Diaz Perlas, Camille Villequey, Tamara Maric, Kaycie Marie Butler, Christina Lamers

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 ...

2021

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

Christian Heinis, Xudong Kong, Vanessa Carle, Cristina Diaz Perlas, Kaycie Marie Butler

The success of phage display, used for developing target-specific binders based on peptides and proteins, depends on the size and diversity of the library screened, but generating large libraries of phage-encoded polypeptides remains challenging. New pepti ...

2020

De novo development of proteolytically resistant therapeutic peptides for oral administration

Christian Heinis, Luciano Andres Abriata, Florence Pojer, Xudong Kong, Vanessa Carle, Kaycie Marie Butler, Jun Moriya

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 ...

2020

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

Christian Heinis, Gerardo Turcatti, Julien Bortoli Chapalay, Alessandro Angelini, Alessandro Zorzi, Jonathan Patrice Vesin, Ganesh Kumar Mothukuri, Sangram Shivdas Kale, Kaycie Marie Butler, Carl Leonard Stenbratt

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 ...

2020

Engineered peptide macrocycles can inhibit matrix metalloproteinases with high selectivity

Christian Heinis, Xudong Kong, Jonas Alfred Karl Wilbs, Jeremy Touati, Maola Khan Mohammad Golam, Michal Sabisz, Alice Baumann, Kaycie Marie Butler

Matrix metalloproteinases (MMPs) are zinc‐dependent endopeptidases at the intersection of health and disease due to their involvement in processes such as tissue repair and immunity as well as cancer and inflammation. Because of the high structural conserv ...

2019

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

Christian Heinis, Kaycie Marie Butler

Naturally evolved peptides, such as the hormone oxytocin or the anti-bacterial vancomycin, have seen decades of success as powerful therapeutics due to many of the favorable properties of peptides. Not every desired target has a naturally occurring bioacti ...

SWISS CHEMICAL SOC2018

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

Christian Heinis, Alessandro Zorzi, Jonas Alfred Karl Wilbs, Simon Jan Middendorp, Kaycie Marie Butler

The rapid renal clearance of peptides in vivo limits this attractive platform for the treatment of a broad range of diseases that require prolonged drug half-lives. An intriguing approach for extending peptide circulation times works through a 'piggy-back' ...

Nature Research2017

Phage Selection of Cyclic Peptides for Application in Research and Drug Development

Christian Heinis, Xudong Kong, Kaycie Marie Butler

Cyclic peptides can bind to protein targets with high affinities and selectivities, which makes them an attractive modality for the development of research reagents and therapeutics. Additional properties, including low inherent toxicity, efficient chemica ...

2017

Cyclic peptide therapeutics: past, present and future

Christian Heinis, Alessandro Zorzi, Kaycie Marie Butler

Cyclic peptides combine several favorable properties such as good binding affinity, target selectivity and low toxicity that make them an attractive modality for the development of therapeutics. Over 40 cyclic peptide drugs are currently in clinical use an ...

2017