title: Novel p65 binding glucocorticoid-induced leucine zipper peptide suppresses experimental autoimmune encephalomyelitis.
abstract: Multiple sclerosis (MS) is a neurological disease characterized by inflammatory demyelination in the brain and spinal cord. The immune-mediated inflammation involves well orchestrated intermolecular interactions that exhibit rapid binding kinetics. The binding interfaces of transient interactions frequently include proline residues that favor an extended conformation for molecular recognition. Linear interface peptides are excellent lead inhibitors of specific protein-protein interactions because only small segments of the interface contribute to the binding. Glucocorticoid-induced leucine zipper (GILZ), a recently identified molecule exhibits potent anti-inflammatory properties. Mechanistically, a proline-rich segment in the carboxyl terminus of GILZ physically binds the p65 subunit of nuclear factor-κB and inhibits the transactivation of inflammatory cytokines. Integrating knowledge derived from the mechanism of action of GILZ with in silico structure prediction identified an immunomodulatory peptide, the GILZ-P. Treatment with GILZ-P exhibited therapeutic efficacy in experimental autoimmune encephalomyelitis, a model for human MS.
authors.affiliation: Department of Oral Pathology, Medicine and Radiology, School of Dentistry, Indiana University-Purdue University Indianapolis, Indianapolis, Indiana 46202, USA. mysriniv@iupui.edu
authors.forename: Mythily
authors.initials: M
authors.lastname: Srinivasan
authors.forename: Srihari
authors.initials: S
authors.lastname: Janardhanam
mesh_terms: D000818:Animals; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy / Q000378:metabolism; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D051996:Transcription Factor RelA / Q000037:antagonists & inhibitors / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry / Q000494:pharmacology
chemical_list: C498608:Dsip1 protein, mouse; D007155:Immunologic Factors; D010455:Peptides; C498144:Rela protein, mouse; D051996:Transcription Factor RelA; D014157:Transcription Factors