title: Engineering S-protein fragments of bovine ribonuclease A for targeted drug delivery.
abstract: High affinity interaction between S-protein and S-peptide fragments of bovine pancreatic RNase A has been recently used for construction of molecular vehicles for targeted drug delivery. The vehicle is assembled as a complex of drug carrier conjugated S-protein with S-peptide-tagged targeting protein. To avoid random chemical crosslinking of drug carriers to S-protein, we constructed a mutant 16-124aa fragment of RNase A in which 122ala is replaced with a cysteine residue. The mutant and the corresponding wild type fragments expressed in Escherichia coli are refolded into functional conformations only in the presence of S-peptide. After the removal of S-peptide, both fragments retain the ability to bind S-peptide and S-peptide-tagged proteins. The 122cys residue in the mutant fragment is available for site-specific conjugation.
authors.affiliation: SibTech Inc., 705 North Mountain Road, Newington, CT 06111, USA. mbacker@sibtech.com
authors.forename: Marina V
authors.initials: MV
authors.lastname: Backer
authors.forename: Timur I
authors.initials: TI
authors.lastname: Gaynutdinov
authors.forename: Renee
authors.initials: R
authors.lastname: Aloise
authors.forename: Kristen
authors.initials: K
authors.lastname: Przekop
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Backer
mesh_terms: D000818:Animals; D002417:Cattle; D016503:Drug Delivery Systems / Q000379:methods*; D004926:Escherichia coli / Q000235:genetics; D009154:Mutation; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D015202:Protein Engineering / Q000379:methods*; D017510:Protein Folding; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012259:Ribonuclease, Pancreatic / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*
chemical_list: D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D012259:Ribonuclease, Pancreatic