Publications de Alessandro Angelini

Large Libraries of Structurally Diverse Macrocycles Suitable for Membrane Permeation

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

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

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

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

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

Molecular analysis and therapeutic applications of human serum albumin-fatty acid interactions

Alessandro Angelini, Alessandro Zorzi, Sara Linciano

Human serum albumin (hSA) is the major carrier protein for fatty acids (FAs) in plasma. Its ability to bind multiple FA moieties with moderate to high affinity has inspired the use of FA conjugation as a safe and natural platform to generate long-lasting t ...

ELSEVIER2022

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

Non-covalent albumin-binding ligands for extending the circulating half-life of small biotherapeutics

Alessandro Angelini, Alessandro Zorzi, Sara Linciano

Peptides and small protein scaffolds are gaining increasing interest as therapeutics. Similarly to full-length antibodies, they can bind a target with a high binding affinity and specificity while remaining small enough to diffuse into tissues. However, de ...

ROYAL SOC CHEMISTRY2019

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

Christian Heinis, Alessandro Angelini, Stephane Kontos, Lisa Pollaro, Sandeep Raghunathan, Julia Morales Sanfrutos

Monoclonal antibodies have long in vivo half-lives and reach high concentrations in tumors but cannot access all regions in the tissue, whereas smaller ligands such as peptides distribute better but are limited by low concentrations due to fast renal clear ...

Amer Assoc Cancer Research2015

Polypeptide inhibitors of urokinase type plasminogen activator

Christian Heinis, Alessandro Angelini

A conjugate which is capable of specific binding to and inhibition of urokinase-type plasminigen activator (UPA) comprising a polypeptide molecule and a scaffold molecule, wherein said polypeptide molecule is attached to said scaffold molecule by at least ...

2013

Phage display libraries of differently sized bicyclic peptides

Christian Heinis, Inmaculada Rentero Rebollo, Alessandro Angelini

Phage selections with combinatorial libraries of uniformly sized bicyclic peptides have recently yielded potent and selective binders of several protein targets. In this work we varied in a combinatorial fashion the ring sizes of bicyclic peptides in phage ...

Royal Soc Chemistry2013

Boosting the Sensitivity of Ligand-Protein Screening by NMR of Long-Lived States

Geoffrey Bodenhausen, Christian Heinis, Aurélien Bornet, Inmaculada Rentero Rebollo, Alessandro Angelini, Simone Ulzega, Nicola Salvi, Roberto Buratto

A new NMR method for the study of ligand protein interactions exploits the unusual lifetimes of long-lived states (LLSs). The new method provides better contrast between bound and free ligands and requires a protein-ligand ratio ca. 25 times lower than for ...

2012

Structurally Diverse Cyclisation Linkers Impose Different Backbone Conformations in Bicyclic Peptides

Christian Heinis, Alessandro Angelini, Shiyu Chen, Julia Morales Sanfrutos

Combinatorial libraries of structurally diverse peptide macrocycles offer a rich source for the development of high-affinity ligands to targets of interest. In this work we have developed linkers for the generation of genetically encoded bicyclic peptides ...

2012