title: Linear biocompatible glyco-polyamidoamines as dual action mode virus infection inhibitors with potential as broad-spectrum microbicides for sexually transmitted diseases.
abstract: The initial steps of viral infections are mediated by interactions between viral proteins and cellular receptors. Blocking the latter with high-affinity ligands may inhibit infection. DC-SIGN, a C-type lectin receptor expressed by immature dendritic cells and macrophages, mediates human immunodeficiency virus (HIV) infection by recognizing mannose clusters on the HIV-1 gp120 envelope glycoprotein. Mannosylated glycodendrimers act as HIV entry inhibitors thanks to their ability to block this receptor. Previously, an amphoteric, but prevailingly cationic polyamidoamine named AGMA1 proved effective as infection inhibitor for several heparan sulfate proteoglycan-dependent viruses, such as human papilloma virus HPV-16 and herpes simplex virus HSV-2. An amphoteric, but prevailingly anionic PAA named ISA23 proved inactive. It was speculated that the substitution of mannosylated units for a limited percentage of AGMA1 repeating units, while imparting anti-HIV activity, would preserve the fundamentals of its HPV-16 and HSV-2 infection inhibitory activity. In this work, four biocompatible linear PAAs carrying different amounts of mannosyl-triazolyl pendants, Man-ISA7, Man-ISA14, Man-AGMA6.5 and Man-AGMA14.5, were prepared by reaction of 2-(azidoethyl)-α-D-mannopyranoside and differently propargyl-substituted AGMA1 and ISA23. All mannosylated PAAs inhibited HIV infection. Both Man-AGMA6.5 and Man-AGMA14.5 maintained the HPV-16 and HSV-2 activity of the parent polymer, proving broad-spectrum, dual action mode virus infection inhibitors.
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Milano, via C. Golgi 19, 20133 Milan, Italy.
authors.forename: Nicolò
authors.initials: N
authors.lastname: Mauro
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Milano, via C. Golgi 19, 20133 Milan, Italy.|Consorzio Interuniversitario di Scienza e Tecnologia dei Materiali, via G. Giusti 9, 56121 Firenze, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Ferruti
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Milano, via C. Golgi 19, 20133 Milan, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Ranucci
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Milano, via C. Golgi 19, 20133 Milan, Italy.
authors.forename: Amedea
authors.initials: A
authors.lastname: Manfredi
authors.affiliation: Department of Biomedical and Clinical Sciences "Sacco", University of Milan, via G. B. Grassi 74, 20157 Milan, Italy.
authors.forename: Angela
authors.initials: A
authors.lastname: Berzi
authors.affiliation: Department of Medical, Surgical and Transplants Physiopathology, University of Milan, via Fratelli Cervi 93, 20090 Segrate, Milan, and Don C. Gnocchi Foundation IRCCS, Via Capecelatro 66, 20148 Milan, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Clerici
authors.affiliation: Dipartimento di Scienze Cliniche e Biologiche, Università di Torino, Azienda Ospedaliero Universitaria S. Luigi Gonzaga, via Regione Gonzole 10, 10043 Orbassano, Torino, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Cagno
authors.affiliation: Dipartimento di Scienze Cliniche e Biologiche, Università di Torino, Azienda Ospedaliero Universitaria S. Luigi Gonzaga, via Regione Gonzole 10, 10043 Orbassano, Torino, Italy.
authors.forename: David
authors.initials: D
authors.lastname: Lembo
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Milano, via C. Golgi 19, 20133 Milan, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Palmioli
authors.affiliation: Dipartimento di Chimica, Università degli Studi di Milano, via C. Golgi 19, 20133 Milan, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Sattin
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D001672:Biocompatible Materials / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D001681:Biological Assay; D015658:HIV Infections / Q000821:virology; D015497:HIV-1 / Q000187:drug effects; D006367:HeLa Cells; D018258:Herpesvirus 2, Human / Q000187:drug effects; D052162:Human papillomavirus 16 / Q000187:drug effects; D006801:Humans; D008358:Mannose / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D008970:Molecular Weight; D011073:Polyamines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D012749:Sexually Transmitted Diseases / Q000188:drug therapy* / Q000821:virology
chemical_list: D000998:Antiviral Agents; D001672:Biocompatible Materials; C531249:Poly(amidoamine); D011073:Polyamines; D008358:Mannose