title: Computational design of a β-peptide that targets transmembrane helices.
abstract: The design of β-peptide foldamers targeting the transmembrane (TM) domains of complex natural membrane proteins has been a formidable challenge. A series of β-peptides was designed to stably insert in TM orientations in phospholipid bilayers. Their secondary structures and orientation in the phospholipid bilayer was characterized using biophysical methods. Computational methods were then devised to design a β-peptide that targeted a TM helix of the integrin α(IIb)β(3). The designed peptide (β-CHAMP) interacts with the isolated target TM domain of the protein and activates the intact integrin in vitro.
authors.affiliation: Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Shandler
authors.forename: Ivan V
authors.initials: IV
authors.lastname: Korendovych
authors.forename: David T
authors.initials: DT
authors.lastname: Moore
authors.forename: Kathryn B
authors.initials: KB
authors.lastname: Smith-Dupont
authors.forename: Craig N
authors.initials: CN
authors.lastname: Streu
authors.forename: Rustem I
authors.initials: RI
authors.lastname: Litvinov
authors.forename: Paul C
authors.initials: PC
authors.lastname: Billings
authors.forename: Feng
authors.initials: F
authors.lastname: Gai
authors.forename: Joel S
authors.initials: JS
authors.lastname: Bennett
authors.forename: William F
authors.initials: WF
authors.lastname: DeGrado
mesh_terms: D000595:Amino Acid Sequence; D017076:Computer-Aided Design; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism*; D011485:Protein Binding; D017433:Protein Structure, Secondary
chemical_list: D010455:Peptides; D019039:Platelet Glycoprotein GPIIb-IIIa Complex