title: Inhibitors of the interactions between HIV-1 IN and the cofactor LEDGF/p75.
abstract: The replication cycle of human immunodeficiency virus type 1 (HIV-1) is a complex multistep process that depends on both viral and host cell factors. The nuclear protein lens epithelium-derived growth factor (LEDGF/p75) is a multidomain protein, present in host cells, which plays an important role in the integration process. LEDGF/p75 not only binds HIV-1 integrase (IN) at its IN binding domain (IBD) but also contains several motifs that function in DNA and chromatin binding. The demonstrated importance of the association between IN and LEDGF/p75 in HIV-1 integration suggests the possibility that this protein-protein interaction (PPI) could be exploited as an antiviral target. We describe herein the progress to date in developing inhibitors of this promising target.
authors.affiliation: Dipartimento Farmaco-Chimico, Università degli Studi di Messina, Viale Annunziata, 98168 Messina, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: De Luca
authors.forename: Stefania
authors.initials: S
authors.lastname: Ferro
authors.forename: Francesca
authors.initials: F
authors.lastname: Morreale
authors.forename: Sara
authors.initials: S
authors.lastname: De Grazia
authors.forename: Alba
authors.initials: A
authors.lastname: Chimirri
mesh_terms: D001565:Benzoates / Q000737:chemistry / Q000494:pharmacology; D019427:HIV Integrase / Q000737:chemistry* / Q000378:metabolism; D019428:HIV Integrase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D015497:HIV-1 / Q000201:enzymology; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000737:chemistry* / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology; D054730:Protein Interaction Domains and Motifs / Q000187:drug effects; D011804:Quinolines / Q000737:chemistry / Q000494:pharmacology; D045162:Thiazolidinediones / Q000737:chemistry / Q000494:pharmacology
chemical_list: C531217:4-((5-bromo-4-((2,4-dioxo-3-(2-oxo-2-phenylethyl)-1,3-thiazolidin-5-ylidene)methyl)-2-ethoxyphenoxy)methyl)benzoic acid; D001565:Benzoates; D019428:HIV Integrase Inhibitors; D007211:Indoles; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D011804:Quinolines; D045162:Thiazolidinediones; C119380:lens epithelium-derived growth factor; D019427:HIV Integrase; C514801:p31 integrase protein, Human immunodeficiency virus 1