title: Identification of three novel peptides that inhibit CD40-CD154 interaction.
abstract: The CD40-CD154 interaction is an attractive target for therapeutic intervention in various autoimmune disorders, including rheumatoid arthritis, systemic lupus erythematosus (SLE), multiple sclerosis, and myasthenia gravis. In this study, to develop a new disruption strategy of the CD40-CD154 interaction, we screened for peptides with inhibitory effects on such ligation. 2 x 10(11) phage display libraries displaying liner peptides of 12-mer amino acids were screened by CD40-Ig binding assay and eight phages which expressed a different respective peptide (40BP-1 to -8) were able to specifically bind to CD40. Competitive inhibition analyses showed that 3 of the 8 peptides (40BP-N1-1 - APELPNMTPSWT; 40BP-N1-2 - APRPHTSYSPLP; and 40BP-N1-3 - GMTAPPPPRLTQ) blocked CD40-CD154 interaction when used at high concentrations. A consensus sequence (APxPPxxT) was conserved in these three peptides. These peptides may constitute a useful and novel strategy for the inhibition of the interaction between CD40 and CD154 molecules.
authors.affiliation: Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, 305-8575, Japan.
authors.forename: Minetake
authors.initials: M
authors.lastname: Kitagawa
authors.forename: Daisuke
authors.initials: D
authors.lastname: Goto
authors.forename: Mizuko
authors.initials: M
authors.lastname: Mamura
authors.forename: Isao
authors.initials: I
authors.lastname: Matsumoto
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ito
authors.forename: Akito
authors.initials: A
authors.lastname: Tsutsumi
authors.forename: Takayuki
authors.initials: T
authors.lastname: Sumida