A General Synthetic Approach for Designing Epitope Targeted Macrocyclic Peptide Ligands.
نویسندگان
چکیده
We describe a general synthetic strategy for developing high-affinity peptide binders against specific epitopes of challenging protein biomarkers. The epitope of interest is synthesized as a polypeptide, with a detection biotin tag and a strategically placed azide (or alkyne) presenting amino acid. This synthetic epitope (SynEp) is incubated with a library of complementary alkyne or azide presenting peptides. Library elements that bind the SynEp in the correct orientation undergo the Huisgen cycloaddition, and are covalently linked to the SynEp. Hit peptides are tested against the full-length protein to identify the best binder. We describe development of epitope-targeted linear or macrocycle peptide ligands against 12 different diagnostic or therapeutic analytes. The general epitope targeting capability for these low molecular weight synthetic ligands enables a range of therapeutic and diagnostic applications, similar to those of monoclonal antibodies.
منابع مشابه
Expression of an epitope-based recombinant vaccine against Foot and Mouth Disease (FMDV) in tobacco plant (Nicotiana tabacum)
Regarding high potential of green plants for development of recombinant vaccines, this research was conducted to evaluate expression of a novel recombinant vaccines against Foot and Mouth Disease (FMDV) in tobacco plant. For this purpose, a synthetic gene encoding 129-169 amino acids of foot and mouth disease virus capsid protein VP1 was transferred to tobacco plant via Agrobacterium-mediated g...
متن کاملSubunit disassembly and inhibition of TNFα by a semi-synthetic bicyclic peptide
Macrocyclic peptides are potentially a source of powerful drugs, but their de novo discovery remains challenging. Here we describe the discovery of a high-affinity (Kd = 10 nM) peptide macrocycle (M21) against human tumor necrosis factor-alpha (hTNFα), a key drug target in the treatment of inflammatory disorders, directly from diverse semi-synthetic phage peptide repertoires. The bicyclic pepti...
متن کاملIn-silico Designing of Immunogenic Construct Based on Peptide Epitopes Using Immuno-informatics Tools Against Tuberculosis
Background and Aim: Mycobacterium tuberculosis is a health problem in countries. Despite the global prevalence of tuberculosis and the lack of appropriate drugs, further progress is still needed with the help of modern methods of preparing epitope-based vaccines for tuberculosis. Materials and Methods: In this study, specific T and B cell epitopes required for producing chimeric vaccines with ...
متن کاملA Novel Multi-Epitope Vaccine For Cross Protection Against Hepatitis C Virus (HCV): An Immunoinformatics Approach
Background: Hepatitis C virus (HCV) causes acute and chronic human hepatitis infections. Due to the high genetic diversity and high rates of mutations in the genetic material so far there is no approved vaccine against HCV. Materials and Methods: The aim of this study was to determination B and T cell conserved epitopes of E1 and E2 proteins from HCV and construction of a chimeric pepti...
متن کاملProduction and Evaluation of Specific Single-Chain Antibodies against CTLA-4 for Cancer-Targeted Therapy
Background: Cytotoxic T lymphocyte–associated antigen 4 (CTLA-4) molecules are expressed on T-cells and inhibit their function by inhibiting activation of subsequent T-cell molecular pathways. Blocking of CTLA-4 inhibits the growth of malignant tumor cells. Anti-CTLA-4 monoclonal antibodies activate the immune system against cancer. Due to several advantages of single-chain antibodi...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Angewandte Chemie
دوره 54 45 شماره
صفحات -
تاریخ انتشار 2015