Schmidt, Florian and Rosnizeck, Ina C. and Spoerner, Michael and Kalbitzer, Hans Robert and Koenig, Burkhard (2011) Zinc(II)cyclen-peptide conjugates interacting with the weak effector binding state of Ras. INORGANICA CHIMICA ACTA, 365 (1). pp. 38-48. ISSN 0020-1693, 1873-3255
Full text not available from this repository. (Request a copy)Abstract
Zinc(II)cyclen-peptide hybrid compounds and bis-zinc(II)cyclen complexes are prepared as potential binders of the guanine nucleotide binding protein Ras, an important molecular switch in cellular signal transduction. The design of the compounds is based on the previous observation that zinc(II)cyclen complexes could serve as lead compounds for inhibitors of Ras-effector interaction and thus be able to interrupt Ras induced signal transduction. Zinc(II)cyclen selectively stabilizes conformational state 1 of active Ras, a conformational state with drastically decreased affinity to effector proteins like Raf-kinase. To achieve higher binding affinities of such Ras-Raf interaction inhibitors, zinc(II)cyclen conjugates with short peptides, derived from the sequence of the Ras-activator SOS, were prepared by solid phase synthesis protocols. Dinuclear bis-zinc(II)cyclen complexes were obtained from alkyne-azide cycloaddition reactions. NMR investigations of the prepared compounds revealed that the peptide conjugates do not lead to an increase in Ras binding affinity of the metal complex-peptide conjugates. The dinuclear zinc complexes lead to an immediate precipitation of the protein prohibiting spectroscopic investigations of their binding. (C) 2010 Elsevier B.V. All rights reserved.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | PROTEIN-PROTEIN INTERACTIONS; SOLID-PHASE SYNTHESIS; METAL-COMPLEX; SUPRAMOLECULAR CHEMISTRY; TERMINAL ALKYNES; PEPTIDES; COOPERATIVITY; MULTIVALENCY; SPECTROSCOPY; DERIVATIVES; Ras protein; Zinc cyclen; Protein-protein inhibition; Metal complex; NMR |
| Subjects: | 500 Science > 540 Chemistry & allied sciences 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biophysik und physikalische Biochemie > Prof. Dr. Dr. Hans Robert Kalbitzer Chemistry and Pharmacy > Institut für Organische Chemie > Lehrstuhl Prof. Dr. Burkhard König |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 29 Jun 2020 07:23 |
| Last Modified: | 29 Jun 2020 07:23 |
| URI: | https://pred.uni-regensburg.de/id/eprint/21396 |
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