Fibrin specific peptides derived by phage display: characterization of peptides and conjugates for imaging.

Published

Journal Article

Peptides that bind to fibrin but not to fibrinogen or serum albumin were selected from phage display libraries as targeting moieties for thrombus molecular imaging probes. Three classes of cyclic peptides (cyclized via disulfide bond between two Cys) were identified with consensus sequences XArXCPY(G/D)LCArIX (Ar = aromatic, Tn6), X(2)CXYYGTCLX (Tn7), and NHGCYNSYGVPYCDYS (Tn10). These peptides bound to fibrin at ∼2 sites with K(d) = 4.1 μM, 4.0 μM, and 8.7 μM, respectively, whereas binding to fibrinogen was at least 100-fold weaker. The peptides also bind to the fibrin degradation product DD(E) with similar affinity to that measured for fibrin. The Tn7 and Tn10 peptides bind to the same site on fibrin, while the Tn6 peptides bind to a unique site. Alanine scanning identified the N- and C-terminal ends of the Tn6 and Tn7 peptides as most tolerant to modification. Peptide conjugates with either fluorescein or diethylenetriaminepentaaceto gadolinium(III) (GdDTPA) at the N-terminus were prepared for potential imaging applications, and these retained fibrin binding affinity and specificity in plasma. Relaxivity and binding studies on the GdDTPA derivatives revealed that an N-terminal glycyl linker had a modest effect on fibrin affinity but resulted in lower fibrin-bound relaxivity.

Full Text

Duke Authors

Cited Authors

  • Kolodziej, AF; Nair, SA; Graham, P; McMurry, TJ; Ladner, RC; Wescott, C; Sexton, DJ; Caravan, P

Published Date

  • March 21, 2012

Published In

Volume / Issue

  • 23 / 3

Start / End Page

  • 548 - 556

PubMed ID

  • 22263840

Pubmed Central ID

  • 22263840

Electronic International Standard Serial Number (EISSN)

  • 1520-4812

Digital Object Identifier (DOI)

  • 10.1021/bc200613e

Language

  • eng

Conference Location

  • United States