Mapping the X+1 binding site of the Grb2-SH2 domain with α,α-disubstituted cyclic α-amino acids

Bioorganic and Medicinal Chemistry Letters

Volumn 9, Issue 20, 1999, Pages 2915-2920

  García Echeverría, Carlos ^a   Gay, Brigitte ^a   Rahuel, Joseph ^b   Furet, Pascal ^a  

^a NOVARTIS PHARMA AG   (Switzerland)

^b UNIVERSITY HOSPITAL BASEL   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA AMINO ACID; PHOSPHOPEPTIDE;

ARTICLE; BINDING SITE; COMPETITIVE INHIBITION; PEPTIDE MAPPING; STRUCTURE ACTIVITY RELATION; SYNTHESIS;

ADAPTOR PROTEINS, SIGNAL TRANSDUCING; AMINO ACIDS, CYCLIC; BINDING SITES; GRB2 ADAPTOR PROTEIN; MODELS, MOLECULAR; PROTEINS; SRC HOMOLOGY DOMAINS;

EID: 0033581557     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(99)00501-6     Document Type: Article

References (27)

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10. For coupling conditions for the incorporation of this amino acid in solid-phase peptide chemistry, see: García- Echeverría, C. Lett. Pept. Sci. 1995, 2, 369.
11. For a side-reaction, see: García-Echeverría, C. Lett. Pept. Sci. 1995, 2, 93.
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14. 1). The reference phosphopeptides 6 and 7 were reported in ref. 11.
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17. 6c amino acid was built with the amino functionality adopting an axial position as observed by X-ray crystallography (Valle, G.; Crisma, M. Toniolo, C.; Sen, M.; Sukumar, M.; Balaram, P. J. Chem. Soc. Perkin Trans. II 1988, 393).
18. 7c was given a twist-chair conformation since it is the most frequently observed in X-ray structures of peptides containing this amino acid (Benedetti, E.; Di Blasio, B.; Iacovino, R.; Menchise, V.; Saviano, M.; Pedone, C.; Bonora, G.M.; Ettorre, A.; Graci, L.; Formaggio, F.; Crisma, M.; Valle, G.; Toniolo, C. J. Chem. Soc. Perkin Trans. 1997, 2, 2023).
19. nc amino acids were taken from X-ray structures and the rest of the peptide was not modified. The models were constructed using Macromodel (Mohamadi, F.; Richards, N.G.; Guida, W.C.; Liskamp, R.; Lipton, M.; Caufield, C.; Chang, G.; Hendrickson, T.; Still, W.C. J.Comp.Chem. 1990, 11, 440-467).
20. For the nomenclature of the SH2 domain residues see: Lee, C.H.; Kominos, D.; Jacques, S.; Margolis, B.; Schlessinger, J.; Shoelson, S.E.; Kuriyan, J. Structure 1994, 2, 423.
21. Gould, R.O.; Gray, A.M.; Taylor, P.; Walkinshaw, M.D. J. Am. Chem. Soc. 1985, 107, 5921.
22. Li, A.J.; Nussinov, R. Proteins 1998, 32, 111.
23. Benedetti, E.; Di Blasio, B.; Pavone, V.; Pedone, C.; Santini, A.; Barone, V.; Fraternali, F.; Lelj, F.; Bavoso, A.; Crisma, M.; Toniolo, C. Int. J. Bio. Macromol., 1989, 11, 353.
24. Dihedral angles for the position i + 2 of a type I or II β-turn: Φ = ±90°, Ψ = 0°.
25. Dihedral angles for the position i + 1 of a type I β-turn: Φ = -60°, Ψ = -30°.
26. At the time this manuscript was submitted, Prof. C. Toniolo has informed us that the "Acnc scan concept" was explicitly mentioned in a publication from his group: Savinna, M. et al. Biopolymers, 1999, in press.
27. Furet, P.; García-Echeverría, C.; Gay, B.; Schoepfer, J.; Zeller, M.; Rahuel, J. J. Med. Chem., 1999, 13, 2358.