A Powerful Combinatorial Screen to Identify High-Affinity Terbium(III)-Binding Peptides

ChemBioChem ◽  
2003 ◽  
Vol 4 (4) ◽  
pp. 272-276 ◽  
Author(s):  
Mark Nitz ◽  
Katherine J. Franz ◽  
Rebecca L. Maglathlin ◽  
Barbara Imperiali
Keyword(s):  
High Affinity ◽  
Binding Peptides

Novel concatameric heparin-binding peptides reverse heparin and low-molecular-weight heparin anticoagulant activities in patient plasma in vitro and in rats in vivo

Blood ◽  
2004 ◽  
Vol 103 (4) ◽  
pp. 1356-1363 ◽  
Author(s):  
Barbara P. Schick ◽  
David Maslow ◽  
Adrianna Moshinski ◽  
James D. San Antonio
Keyword(s):  
Molecular Weight ◽  
Low Molecular Weight Heparin ◽  
Tandem Repeats ◽  
Factor Xa ◽  
Low Molecular Weight ◽  
Heparin Binding ◽  
High Affinity ◽  
Binding Peptides

Abstract Patients given unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) for prophylaxis or treatment of thrombosis sometimes suffer serious bleeding. We showed previously that peptides containing 3 or more tandem repeats of heparin-binding consensus sequences have high affinity for LMWH and neutralize LMWH (enoxaparin) in vivo in rats and in vitro in citrate. We have now modified the (ARKKAAKA)n tandem repeat peptides by cyclization or by inclusion of hydrophobic tails or cysteines to promote multimerization. These peptides exhibit high-affinity binding to LMWH (dissociation constant [Kd], ≈ 50 nM), similar potencies in neutralizing anti–Factor Xa activity of UFH and enoxaparin added to normal plasma in vitro, and efficacy equivalent to or greater than protamine. Peptide (ARKKAAKA)3VLVLVLVL was most effective in all plasmas from enoxaparin-treated patients, and was 4- to 20-fold more effective than protamine. Several other peptide structures were effective in some patients' plasmas. All high-affinity peptides reversed inhibition of thrombin-induced clot formation by UFH. These peptides (1 mg/300 g rat) neutralized 1 U/mL anti–Factor Xa activity of enoxaparin in rats within 1 to 2 minutes. Direct blood pressure and heart rate measurements showed little or no hemodynamic effect. These heparin-binding peptides, singly or in combination, are potential candidates for clinical reversal of UFH and LMWH in humans.

scholarly journals Efficient Identification of Novel Hla-A*0201–Presented Cytotoxic T Lymphocyte Epitopes in the Widely Expressed Tumor Antigen Prame by Proteasome-Mediated Digestion Analysis

2001 ◽  
Vol 193 (1) ◽  
pp. 73-88 ◽  
Author(s):  
Jan H. Kessler ◽  
Nico J. Beekman ◽  
Sandra A. Bres-Vloemans ◽  
Pauline Verdijk ◽  
Peter A. van Veelen ◽  
...  
Keyword(s):  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Epitope Prediction ◽  
Binding Prediction ◽  
Ctl Epitopes ◽  
High Affinity ◽  
Tumor Associated Antigen ◽  
Immunotherapy Of Cancer ◽  
Binding Peptides

We report the efficient identification of four human histocompatibility leukocyte antigen (HLA)-A*0201–presented cytotoxic T lymphocyte (CTL) epitopes in the tumor-associated antigen PRAME using an improved “reverse immunology” strategy. Next to motif-based HLA-A*0201 binding prediction and actual binding and stability assays, analysis of in vitro proteasome-mediated digestions of polypeptides encompassing candidate epitopes was incorporated in the epitope prediction procedure. Proteasome cleavage pattern analysis, in particular determination of correct COOH-terminal cleavage of the putative epitope, allows a far more accurate and selective prediction of CTL epitopes. Only 4 of 19 high affinity HLA-A*0201 binding peptides (21%) were found to be efficiently generated by the proteasome in vitro. This approach avoids laborious CTL response inductions against high affinity binding peptides that are not processed and limits the number of peptides to be assayed for binding. CTL clones induced against the four identified epitopes (VLDGLDVLL, PRA100–108; SLYSFPEPEA, PRA142–151; ALYVDSLFFL, PRA300–309; and SLLQHLIGL, PRA425–433) lysed melanoma, renal cell carcinoma, lung carcinoma, and mammary carcinoma cell lines expressing PRAME and HLA-A*0201. This indicates that these epitopes are expressed on cancer cells of diverse histologic origin, making them attractive targets for immunotherapy of cancer.

High affinity calcium binding peptides from the gills, gut and kidneys of the freshwater eel (Anguilla anguilla)

1978 ◽  
Vol 536 (2) ◽  
pp. 429-432 ◽  
Author(s):  
Peter R. Hearn ◽  
Stephen Tomlinson ◽  
Homa Mellersh ◽  
Christopher J. Kenyon ◽  
Christopher J. Preston ◽  
...  
Keyword(s):  
Calcium Binding ◽  
Anguilla Anguilla ◽  
High Affinity ◽  
Freshwater Eel ◽  
Binding Peptides

Rational Development of Cell-Penetrating High Affinity SH3 Domain Binding Peptides That Selectively Disrupt the Signal Transduction of Crk Family Adapters

1999 ◽  
Vol 886 (1 ANTICANCER MO) ◽  
pp. 289-292 ◽  
Author(s):  
CHRISTIAN KARDINAL ◽  
GUIDO POSERN ◽  
JIE ZHENG ◽  
BEATRICE S. KNUDSEN ◽  
ISMAIL MOAREFI ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Sh3 Domain ◽  
High Affinity ◽  
Rational Development ◽  
Cell Penetrating ◽  
Binding Peptides

scholarly journals Designing high affinity target-binding peptides to HLA-E: a key membrane antigen of multiple myeloma

Aging ◽  
2020 ◽  
Vol 12 (20) ◽  
pp. 20457-20470
Author(s):  
Ying Yang ◽  
Mingli Sun ◽  
Zhaojin Yu ◽  
Jinwei Liu ◽  
Wei Yan ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
High Affinity ◽  
Binding Peptides ◽  
Target Binding

scholarly journals Antibody-guided design and identification of CD25-binding small antibody mimetics using mammalian cell surface display

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kyra See ◽  
Tetsuya Kadonosono ◽  
Kotaro Miyamoto ◽  
Takuya Tsubaki ◽  
Yumi Ota ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Dissociation Constants ◽  
Surface Display ◽  
Interleukin 2 ◽  
Peptide Identification ◽  
Cell Surface Display ◽  
Affinity Maturation ◽  
High Affinity ◽  
Binding Peptides ◽  
Target Binding

AbstractSmall antibody mimetics that contain high-affinity target-binding peptides can be lower cost alternatives to monoclonal antibodies (mAbs). We have recently developed a method to create small antibody mimetics called FLuctuation-regulated Affinity Proteins (FLAPs), which consist of a small protein scaffold with a structurally immobilized target-binding peptide. In this study, to further develop this method, we established a novel screening system for FLAPs called monoclonal antibody-guided peptide identification and engineering (MAGPIE), in which a mAb guides selection in two manners. First, antibody-guided design allows construction of a peptide library that is relatively small in size, but sufficient to identify high-affinity binders in a single selection round. Second, in antibody-guided screening, the fluorescently labeled mAb is used to select mammalian cells that display FLAP candidates with high affinity for the target using fluorescence-activated cell sorting. We demonstrate the reliability and efficacy of MAGPIE using daclizumab, a mAb against human interleukin-2 receptor alpha chain (CD25). Three FLAPs identified by MAGPIE bound CD25 with dissociation constants of approximately 30 nM as measured by biolayer interferometry without undergoing affinity maturation. MAGPIE can be broadly adapted to any mAb to develop small antibody mimetics.

scholarly journals The use of mRNA display to select high-affinity protein-binding peptides

2001 ◽  
Vol 98 (7) ◽  
pp. 3750-3755 ◽  
Author(s):  
D. S. Wilson ◽  
A. D. Keefe ◽  
J. W. Szostak
Keyword(s):  
Protein Binding ◽  
Mrna Display ◽  
High Affinity ◽  
Binding Peptides

scholarly journals Cover Picture: A Powerful Combinatorial Screen to Identify High-Affinity Terbium(III)-Binding Peptides (ChemBioChem 4/2003)

ChemBioChem ◽  
2003 ◽  
Vol 4 (4) ◽  
pp. 241-241
Author(s):  
Mark Nitz ◽  
Katherine J. Franz ◽  
Rebecca L. Maglathlin ◽  
Barbara Imperiali
Keyword(s):  
High Affinity ◽  
Binding Peptides
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