Synthesis of Reagents for the Construction of Hypusine and Deoxyhypusine Peptides and Their Application as Peptidic Antigens
| Autor: | Ralf Müller, Bruce H. McCosar, Raymond J. Bergeron, Richard E. Smith, Hua Yao, Curt O. Zimmerman, William R. Weimar |
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| Rok vydání: | 1998 |
| Předmět: |
Ovalbumin
Stereochemistry medicine.drug_class Enzyme-Linked Immunosorbent Assay chemical and pharmacologic phenomena Peptide CHO Cells Cross Reactions Monoclonal antibody complex mixtures Chemical synthesis Maleimides Mice chemistry.chemical_compound Peptide Initiation Factors Cricetinae Drug Discovery medicine Peptide synthesis Animals Humans Protecting group Hypusine chemistry.chemical_classification Mice Inbred BALB C biology Lysine Antibodies Monoclonal RNA-Binding Proteins Stereoisomerism Biochemistry chemistry Hemocyanins biology.protein Molecular Medicine Haptens Oligopeptides Keyhole limpet hemocyanin Conjugate |
| Zdroj: | Journal of Medicinal Chemistry. 41:3888-3900 |
| ISSN: | 1520-4804 0022-2623 |
| Popis: | Two new synthetic methods which allow access to (2S)-deoxyhypusine, natural (2S,9R)-hypusine, (2S,9S)-hypusine, and deoxyhypusine- and hypusine-containing peptides are described. The methods involve both the construction of a deoxyhypusine reagent in which the alpha-nitrogen protecting group is orthogonal to the N-7 and N-12 protecting groups and an alternate synthesis of our previous hypusine reagent, a synthesis which provides for better stereochemical control at C-9. Synthetic hypusine and deoxyhypusine can be generated from these reagents. The hypusine-containing hexapeptide (Cys-Thr-Gly-Hpu-His-Gly) is conjugated to ovalbumin (OVA), keyhole limpet hemocyanin (KLH), and a bis-maleimide; KLH conjugates are also made with the deoxyhypusine- and lysine-containing hexapeptides. Monoclonal antibodies are generated to the hypusine-containing hexapeptide-OVA conjugate in mice. These are isolated and screened against the hypusine-containing hexapeptide-KLH and hypusine-containing hexapeptide-bis-maleimide conjugates, as well as against the deoxyhypusine-containing and lysine-containing hexapeptide-KLH conjugates. These antibodies may be useful in localizing intracellular hypusine-containing peptides as well as peptides containing hypusine analogues. |
| Databáze: | OpenAIRE |
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