title: Design, synthesis, and in vitro activity of peptidomimetic inhibitors of myeloid differentiation factor 88.
abstract: We describe the design and synthesis of a peptidomimetic library derived from the heptapeptide Ac-RDVLPGT-NH 2, belonging to the Toll/IL-1 receptor (TIR) domain of the adaptor protein MyD88 and effective in inhibiting its homodimerization. The ability of the peptidomimetics to inhibit protein-protein interaction was assessed by yeast 2-hybrid assay and further validated in a mammalian cell system by evaluating the inhibition of NF-kappaB activation, a transcription factor downstream of MyD88 signaling pathway that allows production of essential effector molecules for immune and inflammatory responses.
authors.affiliation: Sigma-Tau Industrie, Pomezia, Italy. nicola.fanto@sigma-tau.it
authors.forename: Nicola
authors.initials: N
authors.lastname: Fantò
authors.forename: Grazia
authors.initials: G
authors.lastname: Gallo
authors.forename: Andrea
authors.initials: A
authors.lastname: Ciacci
authors.forename: Mauro
authors.initials: M
authors.lastname: Semproni
authors.forename: Davide
authors.initials: D
authors.lastname: Vignola
authors.forename: Marco
authors.initials: M
authors.lastname: Quaglia
authors.forename: Valentina
authors.initials: V
authors.lastname: Bombardi
authors.forename: Domenico
authors.initials: D
authors.lastname: Mastroianni
authors.forename: M Pia
authors.initials: MP
authors.lastname: Zibella
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Basile
authors.forename: Marica
authors.initials: M
authors.lastname: Sassano
authors.forename: Vito
authors.initials: V
authors.lastname: Ruggiero
authors.forename: Rita
authors.initials: R
authors.lastname: De Santis
authors.forename: Paolo
authors.initials: P
authors.lastname: Carminati
mesh_terms: D002460:Cell Line; D006801:Humans; D008958:Models, Molecular; D018716:Molecular Mimicry; D053594:Myeloid Differentiation Factor 88 / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D017434:Protein Structure, Tertiary; D017472:Receptors, Interleukin-1 / Q000737:chemistry / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D051193:Toll-Like Receptors / Q000737:chemistry / Q000378:metabolism; D020798:Two-Hybrid System Techniques
chemical_list: D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D009842:Oligopeptides; D017472:Receptors, Interleukin-1; D051193:Toll-Like Receptors