title: Privileged scaffolds for blocking protein-protein interactions: 1,4-disubstituted naphthalene antagonists of transcription factor complex HOX-PBX/DNA.
abstract: Structure-based-design studies, with the crystal structure of the HOXB1-PBX1/DNA transcription factor complex, were used to identify 1,4-disubstituted naphthalenes as potential antagonists. An initial library of 32 analogs was synthesized, two of which were found to be more potent than the reported activity for a 12 amino acid peptide antagonist. Antagonists were also identified of the related BRN1/DNA and BRN2/DNA transcription factor complexes indicating that a 1,4-disubstituted naphthalene may be a privileged scaffold for preparing screening libraries targeting this family of transcription factor complexes.
authors.affiliation: Department of Chemistry, University at Buffalo, The State University of New York, Buffalo, NY 14260-3000, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Ji
authors.forename: Madison
authors.initials: M
authors.lastname: Lee
authors.forename: Steven C
authors.initials: SC
authors.lastname: Pruitt
authors.forename: David G
authors.initials: DG
authors.lastname: Hangauer
mesh_terms: D018360:Crystallography, X-Ray; D004247:DNA / Q000037:antagonists & inhibitors; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D018398:Homeodomain Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D009281:Naphthalenes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D014157:Transcription Factors / Q000037:antagonists & inhibitors*
chemical_list: D004268:DNA-Binding Proteins; C101121:HOXB1 homeodomain protein; D018398:Homeodomain Proteins; D009281:Naphthalenes; D000075062:Pre-B-Cell Leukemia Transcription Factor 1; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; C083400:PBX1 protein, human; D004247:DNA