Publications by authors named "Donatella Invernizzi"

4 Publications

  • Page 1 of 1

A potent integrin antagonist from a small library of cyclic RGD pentapeptide mimics including benzyl-substituted azabicycloalkane amino acids.

ChemMedChem 2008 Oct;3(10):1589-603

Istituto di Scienze e Tecnologie Molecolari, Consiglio Nazionale delle Ricerche, Via Fantoli 16/15, 20138 Milano, Italy.

A small library of cyclic RGD pentapeptide mimics, including benzyl-substituted azabicycloalkane amino acids, was synthesized with the aim of developing active and selective integrin antagonists. In vitro binding assays established one particular compound with affinity for both the alpha(v)beta(3) and the alpha(v)beta(5) integrins. The synthesis in solution and the in vitro screening of these RGD derivatives, as well as the determination of the conformational properties of the integrin ligands by spectroscopic and computational methods are described.
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http://dx.doi.org/10.1002/cmdc.200800143DOI Listing
October 2008

Synthesis of novel DC-SIGN ligands with an alpha-fucosylamide anchor.

Chembiochem 2008 Aug;9(12):1921-30

Dipartimento di Chimica Organica e Industriale and CISI, Università di Milano, via Venezian 21, 20133 Milano, Italy.

The dendritic cell-specific intercellular adhesion molecule (ICAM) 3-grabbing nonintegrin (DC-SIGN) is a C-type lectin that appears to perform several different functions. Besides mediating adhesion between dendritic cells and T lymphocytes, DC-SIGN recognizes several pathogens some of which, including HIV, appear to exploit it to invade host organisms. The intriguing diversity of the roles attributed to DC-SIGN and their therapeutic implications have stimulated the search for new ligands that could be used as biological probes and possibly as lead compounds for drug development. The natural ligands of DC-SIGN consist of mannose oligosaccharides or fucose-containing Lewis-type determinants. Using the known 3D structure of the Lewis-x trisaccharide, we have identified some monovalent alpha-fucosylamides that bind to DC-SIGN with inhibitory constants 0.4-0.5 mM, as determined by SPR, and have characterized their interaction with the protein by STD NMR spectroscopy. This work establishes for the first time alpha-fucosylamides as functional mimics of chemically and enzymatically unstable alpha-fucosides and describes interesting candidates for the preparation of multivalent systems able to block the receptor DC-SIGN with high affinity and with potential biomedical applications.
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http://dx.doi.org/10.1002/cbic.200800139DOI Listing
August 2008

1,2-Mannobioside mimic: synthesis, DC-SIGN interaction by NMR and docking, and antiviral activity.

ChemMedChem 2007 Jul;2(7):1030-6

Departamento de Química Bioorgánica, Instituto de Investigaciones Químicas, CSIC, Américo Vespucio 49, 41092 Sevilla, Spain.

The design and preparation of carbohydrate ligands for DC-SIGN is a topic of high interest because of the role played by this C-type lectin in immunity and infection processes. The low chemical stability of carbohydrates against enzymatic hydrolysis by glycosylases has stimulated the search for new alternatives more stable in vivo. Herein, we present a good alternative for a DC-SIGN ligand based on a mannobioside mimic with a higher enzymatic stability than the corresponding disaccharide. NMR and docking studies have been performed to study the interaction of this mimic with DC-SIGN in solution demonstrating that this pseudomannobioside is a good ligand for this lectin. In vitro studies using an infection model with Ebola pseudotyped virus demonstrates that this compound presents an antiviral activity even better than the corresponding disaccharide and could be an interesting ligand to prepare multivalent systems with higher affinities for DC-SIGN with potential biomedical applications.
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http://dx.doi.org/10.1002/cmdc.200700047DOI Listing
July 2007

Functionalized azabicycloalkane amino acids by nitrone 1,3-dipolar intramolecular cycloaddition.

J Org Chem 2005 May;70(10):4124-32

C.N.R.-Istituto di Scienze e Tecnologie Molecolari, and Centro Interdisciplinare Studi bio-molecolari e applicazioni Industriali, Via Venezian 21, I-20133, Milano, Italy.

[reaction: see text] An efficient and operationally simple method for the synthesis of functionalized azaoxobicyclo[X.3.0]alkane amino acids has been devised. The key step is an intramolecular nitrone cycloaddition on 5-allyl- or 5-homoallylproline that was found to be completely regio- and stereoselective.
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http://dx.doi.org/10.1021/jo0500683DOI Listing
May 2005
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