title: Engineered staphylococcal protein A's IgG-binding domain with cathepsin L inhibitory activity.
abstract: Inhibitory peptide of papain-like cysteine proteases, affinity selected from a random disulfide constrained phage-displayed peptide library, was grafted to staphylococcal protein A's B domain. Scaffold protein was additionally modified in order to allow solvent exposed display of peptide loop. Correct folding of fusion proteins was confirmed by CD-spectroscopy and by the ability to bind the Fc-region of rabbit IgG, a characteristic of parent domain. The recombinant constructs inhibited cathepsin L with inhibitory constants in the low-micromolar range.
authors.affiliation: Faculty of Pharmacy, Department of Pharmaceutical Biology, University of Ljubljana, Askerceva 7, SI-1000 Ljubljana, Slovenia. tomaz.bratkovic@ffa.uni-lj.si
authors.forename: Tomaz
authors.initials: T
authors.lastname: Bratkovic
authors.forename: Ales
authors.initials: A
authors.lastname: Berlec
authors.forename: Tatjana
authors.initials: T
authors.lastname: Popovic
authors.forename: Mojca
authors.initials: M
authors.lastname: Lunder
authors.forename: Samo
authors.initials: S
authors.lastname: Kreft
authors.forename: Uros
authors.initials: U
authors.lastname: Urleb
authors.forename: Borut
authors.initials: B
authors.lastname: Strukelj
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D056668:Cathepsin L; D002403:Cathepsins / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D003546:Cysteine Endopeptidases / Q000737:chemistry*; D004220:Disulfides / Q000737:chemistry; D007074:Immunoglobulin G / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019151:Peptide Library; D011485:Protein Binding; D017510:Protein Folding; D017434:Protein Structure, Tertiary; D011817:Rabbits; D013205:Staphylococcal Protein A / Q000737:chemistry*
chemical_list: D004220:Disulfides; D007074:Immunoglobulin G; D019151:Peptide Library; D013205:Staphylococcal Protein A; D002403:Cathepsins; D003546:Cysteine Endopeptidases; D056668:Cathepsin L