title: A novel hSH3 domain scaffold engineered to bind folded domains in CD2BP2 and HIV capsid protein.
abstract: Engineered protein scaffolds destined to target and inhibit molecular interactions in the context of disease bear great diagnostic and therapeutic potential. Apart from antibodies several alternative scaffolds have been exploited over the years making use of the fact that individual domain families are best suited for certain target families. Here we capitalize on the helically extended SH3 domain hSH3N of the ADAP protein as loop-randomized template that was tested against HIV capsid (CA) protein and the GYF domain of human CD2BP2 as molecular targets. Phage display of mutant proteins resulted in the isolation of variants with changes in all randomized positions compared with wild-type hSH3N. The soluble scaffolds bind with 340 and 600 nM affinity to CA and CD2BP2, respectively, and employ large molecular surfaces to pull out these targets from complex mixtures.
authors.affiliation: Leibniz-Institute for Molecular Pharmacology Robert-Rössle-Str. 10, 13125 Berlin,  Germany.
authors.forename: Kirill
authors.initials: K
authors.lastname: Piotukh
authors.forename: Christian
authors.initials: C
authors.lastname: Freund
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D000595:Amino Acid Sequence; D036022:Capsid Proteins / Q000378:metabolism*; D061505:Cell Surface Display Techniques; D006678:HIV / Q000378:metabolism*; D015658:HIV Infections / Q000175:diagnosis / Q000188:drug therapy; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015202:Protein Engineering; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D018909:src Homology Domains
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C120378:CD2BP2 protein, human; D036022:Capsid Proteins; C106957:FYB1 protein, human; D011994:Recombinant Proteins