Scaffolded Peptidic Libraries and Methods of Making and Screening the Same

摘要

Scaffolded peptidic libraries and methods of screening the same for specific binding to a target protein are provided. Each library includes distinct peptidic compounds that include a scaffold domain and a distinct variable domain. A variety of libraries are provided where each library is based on an underlying peptidic scaffold having a structural motif. In some embodiments, the peptidic scaffold is a small protein having a protein-protein interaction surface. Libraries of polynucleotides that encode a variety of peptidic compounds are provided. These libraries find use in a variety of applications in which specific binding to target molecules, e.g., target proteins is desired. Also provided are methods of making the libraries and methods of screening the libraries for binding to a target.

主权项

1. A library of distinct peptidic compounds, wherein:
each compound of the library comprises a distinct variable domain and a peptidic scaffold domain, wherein the peptidic scaffold domain is selected from the group consisting of: DiGeorge syndrome critical region 8 (DGCR8) dimerization domain; Get5 C-terminal domain; H-NS domain from E. coli; KorB c-terminal dimerization domain; Lsr2 dimerization domain; PKA-RI alpa dimerization/docking domain (bovine); UBA domain of p62; N-terminal domain of SpoVT; Collagen XI trimerization domain; Symfoil 4P trimer (designed beta-trefoil); C-terminal domain of RNA polymerase alpha subunit; EphA2 SAM domain; GRIP domain of Golgin245; SpoOB-Helix hairpin domain; C-terminal domain of Ku; CUE domain of Cue2 protein; DNA helicase RuvA domain; GA domain of protein G; Hirustasin; Thrombomodulin (EGF type domains); Coagulation factor VIIa; PEM-1 like protein; Fasciculin-2; CD46 extracellular domain; Nucleotide exchange factor C-terminal domain; Tudor domain of TDRD3; Transcription antitermination protein NusG; CCL2 chemokine; ThiS protein in complex with ThiF; Chymotrypsin inhibitor; Carboxypeptidase inhibitor; GYF domain of CD2bp2; Cdk regulatory subunit1; CN2 toxin; CHD4-PHD finger domain; GATA type zinc finger; Leech derived tryptase inhibitor; Rhodnin Kazal inhibitor; MHC ClassII p41 fragment; Anti-TRAP; TNF Receptor17 (BCMA); NZF zinc-finger domain; Amaranth alpha amylase inhibitor; Sac7d (Nanofitins); APPI Kunitz domain; Fyn SH3 domain (Fynomers); E3 ubiquitin-protein ligase UBR5; DNA repair endonuclease XPF; Chain B:rad23 hom.B, xpcb domain; Chain B:dsk2-uba domain; Chain C:LEM domain/emerin; Chain A:Protein YBL047C UBA domain; Chains A/B: PKA docking/dimerization domain; Chain C: GspC; Chain A: Phage IF1 attachment protein G3P; Chain A: cd2ap sh3; Chain B: micronemal protein 6, EGF-like domain; Chain B: colicin-A; Chain B: Rubredoxin 2; Chain E: EGF domain of LDLR; Chain I: engineered protease inhibitor, SGPI scaffold; Chain B: engineered hck sh3; N-terminal fragment: NTL9; Brazzein; Insulin growth factor binding protein (IGFBP); Turkey ovomucoid, third domain (OMTKY3); Viscotoxin A1; Chromobox protein homolog 5; Villin headpiece subdomain; and Protein Z domain.