CDK2/cyclinA inhibitors: Targeting the cyclinA recruitment site with small molecules derived from peptide leads

Bioorganic and Medicinal Chemistry Letters

Volumn 16, Issue 6, 2006, Pages 1716-1720

  Castanedo, Georgette ^a   Clark, Kevin ^a   Wang, Shumei ^a   Tsui, Vickie ^a   Wong, Mengling ^a   Nicholas, John ^a   Wickramasinghe, Dineli ^a   Marsters Jr , James C ^a   Sutherlin, Daniel ^a  

^a GENENTECH INC   (United States)

Author keywords

CDK2 cyclinA; Guanidine replacement; Protein protein interaction inhibitor

Indexed keywords

AMINO ACID; CYCLIN A; CYCLIN DEPENDENT KINASE 2 INHIBITOR; GUANIDINE; OCTAPEPTIDE; TETRAPEPTIDE;

AMINO ACID SEQUENCE; ARTICLE; MOLECULAR SIZE; PEPTIDE SYNTHESIS; STRUCTURE ACTIVITY RELATION;

AMINO ACID SUBSTITUTION; CYCLIN A; CYCLIN-DEPENDENT KINASE 2; DRUG DESIGN; ENZYME INHIBITORS; GUANIDINE; HUMANS; MODELS, MOLECULAR; PEPTIDE FRAGMENTS; PROTEIN CONFORMATION;

CYCLINA;

EID: 32044437649     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2005.12.004     Document Type: Article

References (17)

1. A.A. Russo, P.D. Jeffrey, A.K. Patten, J. Massague, and N.P. Pavletich Nature 382 1996 325
2. J.A. Lees, and R.A. Weinberg Proc. Natl. Acad. Sci. U.S.A. 96 1999 4221
3. Y.-N.P. Chen, S.K. Sharma, T.M. Ramsey, L. Jiang, M.S. Martin, K. Baker, P.D. Adams, K.W. Bair, and W.G. Kaelin Proc. Natl. Acad. Sci. U.S.A. 96 1999 4325
4. N. Mendoza, S. Fong, J. Marsters, H. Koeppen, R. Schwall, and D. Wickramasinghe Cancer Res. 63 2003 1020
5. S.K. Sharma, T.M. Ramsey, Y.-N.P. Chen, W. Chen, M.S. Martin, K. Clune, M. Sabio, and K.W. Blair Bioorg. Med. Chem. Lett. 11 2001 2449
6. G.A. Atkinson, A. Cowan, C. McInnes, D.I. Zheleva, P.M. Fisher, and W.C. Chan Bioorg. Med. Chem. Lett. 12 2002 2501
7. C. McInnes, M.J.I. Andrews, D.I. Zheleva, D.P. Lane, and P.M. Fisher Curr. Med. Chem. Anti-Cancer Agents 3 2003 57
8. D.I. Zheleva, C. McInnes, A.-L. Gavine, N.Z. Zhelev, P.M. Fisher, and D.P. Lane J. Peptide Res. 60 2002 257
9. N.R. Brown, M.E.M. Noble, J.A. Endicott, and L.N. Johnson Nat. Cell Biol. 1 1999 438
10. E.D. Lowe, I. Tews, K.Y. Cheng, N.R. Brown, S. Gul, M.E.M. Noble, S.J. Gamblin, and L.N. Johnson Biochemistry 41 2002 15634
11. G. Kontopidis, M.J.I. Andrews, A. Cowan, H. Powers, L. Innes, A. Plater, G. Griffiths, D. Paterson, D.I. Zheleva, D.P. Lane, S. Green, M.D. Walkinshaw, and P.M. Fisher Structure 11 2003 1537
12. P.D. Adams, W.R. Sellers, S.K. Sharma, A.D. Wu, C.M. Nalin, and W.G. Kaelin Mol. Cell. Biol. 16 1996 6623
13. D.Y. Takeda, J.A. Wohlschlegel, and A. Dutta J. Biol. Chem. 276 2001 1993
14. J.A. Wohlschlegel, B.T. Dwyer, D.Y. Takeda, and A. Dutta Mol. Cell. Biol. 21 2001 4868
15. 2). The reactions were diluted 1:10 into kinase stop buffer in the ELISA plate. Phosphorylated Rb was detected with rabbit anti-phospho-Rb (Ser795) followed by (HRP)-linked IgG anti-rabbit antibody. The plate was developed with tetramethylbenzidine as substrate and the absorbance was measured at 450 nm.
16. T. Hayashi, T. Senda, and M. Ogasawara J. Am. Chem. Soc. 122 2000 10716
17. The model was built from co-crystal structures of other peptides and peptidomimetics, and minimized in the CyclinA binding site using Schrodinger's Macromodel program.