| Autor: |
Õrfi, László, Wáczek, Frigyes, Kövesdi, István, Mészáros, György, Idei, Miklós, Horváth, Anikó, Hollósy, Ferenc, Mák, Marianna, Szegedi, Zsolt, Szende, Béla, Kéri, György |
| Zdroj: |
Letters in Peptide Science; Sep1999, Vol. 6 Issue 5/6, p325-333, 9p |
| Abstrakt: |
A parallel combinatorial library of over 1600 compounds has been designed and synthesized for the development of new potential peptidomimetic protein tyrosine kinase (PTK) inhibitor leads. These peptidomimetic molecules are aimed at intervening with the substrate binding site of the pp60 enzyme. The new structures were based on known PTK inhibitors with at least two variously substituted aromatic moieties attached by spacer groups of different length and flexibility. Eleven bis-aryl-type inhibitory compounds were found in the range of 18-100 μM IC concentrations from combinations of 12 different substituents. Molecular modeling of the active compounds showed a characteristic distance of 12-14 Å between the farthest sp carbon atoms of the two aromatic rings. Conformational analysis of several peptide substrates recently found for pp60 PTK showed that the energy-minimized conformers had the same distance between the two aromatic moieties. Several compounds in the library not only showed remarkable PTK inhibitory activity but also a significant apoptosis-inducing effect on HT-29 human colon tumor cells. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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