Discovery of high-affinity peptide binders to BLyS by phage display

被引:26
作者
Fleming, TJ
Sachdeva, M
Delic, M
Beltzer, J
Wescott, CR
Devlin, M
Ladner, RC
Nixon, AE
Roschke, V
Hilbert, DM
Sexton, DJ
机构
[1] Dyax Corp, Cambridge, MA 02139 USA
[2] Human Genome Sci Inc, Rockville, MD 20850 USA
关键词
phage display; BLyS; affinity maturation; ruthenium anisotropy; TNF; Lupus; arthritis;
D O I
10.1002/jmr.722
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
B lymphocyte stimulator (BLyS) is a tumor necrosis factor (TNF) family member and a key regulator of B cell responses. We employed a phage display-based approach to identify peptides that bind BLyS with high selectivity and affinity. Sequence analysis of first-generation BLyS-binding peptides revealed two dominant peptide motifs, including one containing a conserved DxLT sequence. Selected linear peptides with this motif were found to bind BLyS with K-D values of 1-3 mu m. In order to improve the binding affinity for BLyS, consensus residues flanking the DxLT sequence were seeded into a second-generation, BLyS affinity maturation library (BAML). BAML phage were subjected to stringent binding competition conditions to select for isolates expressing high-affinity peptide ligands for BLyS. Post-selection analysis of BAML peptide sequences resulted in the identification of a core decapeptide motif (WYDPLTKLWL). Peptides containing this core motif exhibited KD values as low as 26 nm, approximately 100-fold lower than that of first-generation peptides. A fluorescence anisotropy assay was developed to monitor the protein-protein interaction between BLyS labeled with a ruthenium chelate, and TACI-Fc, a soluble form of a BLyS receptor. Using this assay it was found that a BAML peptide disrupts this high-affinity protein-protein interaction. This demonstrates the potential of short peptides for disruption of high affinity cytokine-receptor interactions. Copyright (c) 2004 John Wiley & Sons, Ltd.
引用
收藏
页码:94 / 102
页数:9
相关论文
共 50 条
[11]   A Phage Display Screening Derived Peptide with Affinity for the Adeninyl Moiety [J].
Elmlund, Louise ;
Soderberg, Pernilla ;
Suriyanarayanan, Subramanian ;
Nicholls, Ian A. .
BIOSENSORS-BASEL, 2014, 4 (02) :137-149
[12]   In vitro evolution of an antibody fragment population to find high-affinity hapten binders [J].
Persson, Helena ;
Wallmark, Henrik ;
Ljungars, Anne ;
Hallborn, Johan ;
Ohlin, Mats .
PROTEIN ENGINEERING DESIGN & SELECTION, 2008, 21 (08) :485-493
[13]   The Improved Delivery to Breast Cancer Based on a Novel Nanocarrier Modified with High-Affinity Peptides Discovered by Phage Display [J].
Zhang, Haoran ;
Guo, Zhaoming ;
He, Bing ;
Dai, Wenbing ;
Zhang, Hua ;
Wang, Xueqing ;
Zhang, Qiang .
ADVANCED HEALTHCARE MATERIALS, 2018, 7 (20)
[14]   Peptide phage display [J].
Tang, WG ;
Gan, RB ;
Wang, KY .
PROGRESS IN BIOCHEMISTRY AND BIOPHYSICS, 1997, 24 (03) :203-207
[15]   In vitro affinity screening of protein and peptide binders by megavalent bead surface display [J].
Diamante, Letizia ;
Gatti-Lafranconi, Pietro ;
Schaerli, Yolanda ;
Hollfelder, Florian .
PROTEIN ENGINEERING DESIGN & SELECTION, 2013, 26 (10) :713-724
[16]   Synthesis of a High Affinity Complementary Peptide-Polymer Nanoparticle (NP) Pair Using Phage Display [J].
Lee, Shih-Hui ;
Moody, Issa ;
Zeng, Zhiyang ;
Fleischer, Everly B. ;
Weiss, Gregory A. ;
Shea, Kenneth J. .
ACS APPLIED BIO MATERIALS, 2021, 4 (03) :2704-2712
[17]   Affinity Maturation of an ERBB2-Targeted SPECT Imaging Peptide by In Vivo Phage Display [J].
Benjamin M. Larimer ;
William D. Thomas ;
George P. Smith ;
Susan L. Deutscher .
Molecular Imaging and Biology, 2014, 16 :449-458
[18]   Discovery of Peptide Ligands for Hepatic Stellate Cells Using Phage Display [J].
Chen, Zhijin ;
Jin, Wei ;
Liu, Hao ;
Zhao, Zhen ;
Cheng, Kun .
MOLECULAR PHARMACEUTICS, 2015, 12 (06) :2180-2188
[19]   Peptide Phage Display as a Tool for Drug Discovery: Targeting Membrane Receptors [J].
Molek, Peter ;
Strukelj, Borut ;
Bratkovic, Tomaz .
MOLECULES, 2011, 16 (01) :857-887
[20]   Discovery of High-Affinity Protein Binding Ligands - Backwards [J].
Diehnelt, Chris W. ;
Shah, Miti ;
Gupta, Nidhi ;
Belcher, Paul E. ;
Greving, Matthew P. ;
Stafford, Phillip ;
Johnston, Stephen Albert .
PLOS ONE, 2010, 5 (05)