Synthesis and Biological Evaluation of Protein:Geranylgeranyltransferase I Inhibitors Based on the CaaX Box: Incorporation of Sugar Amino Acids as Dipeptide Isosters
✍ Scribed by Farid El Oualid; Leon Bruining; Ingrid M. Leroy; Louis H. Cohen; Jacques H. van Boom; Gijs A. van der Marel; Herman S. Overkleeft; Mark Overhand
- Publisher
- John Wiley and Sons
- Year
- 2002
- Tongue
- German
- Weight
- 244 KB
- Volume
- 85
- Category
- Article
- ISSN
- 0018-019X
No coin nor oath required. For personal study only.
✦ Synopsis
Dedicated to Professor Dieter Seebach on the occasion of his 65th birthday Two orthogonally protected SAA building blocks were used in the synthesis of eight novel analogues of the CaaX motif present in the natural substrates of protein:geranylgeranyltransferase I (PGGT I), an enzyme involved in the post-translational modification of oncogenic proteins, e.g., Ras K-4B. Remarkably, two compounds, which are stereochemically different at the C(1') position of the SAA residue and at C(2) of the Cys residue, showed comparable activity in a PGGT-1 assay. Our results indicate that both (1,5-cis) and (1,5-trans) SAA building blocks can be used for the development of novel PGGT I inhibitors.