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Synthesis of GTP‐Derived Ras Ligands
Author(s) -
Soulère Laurent,
Aldrich Courtney,
Daumke Oliver,
Gail Robert,
Kissau Lars,
Wittinghofer Alfred,
Waldmann Herbert
Publication year - 2004
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200400133
Subject(s) - gtp' , chemistry , substituent , small molecule , gtpase , combinatorial chemistry , total synthesis , biochemistry , stereochemistry , enzyme
A practical and convenient method for the synthesis of acid‐ and base‐sensitive GTP analogues carrying a further substituent at the terminal phosphate has been developed. Key to the successful synthesis of these potential ligands of the Ras protein is the use of Pd 0 ‐sensitive allyl protecting groups in a one‐pot synthesis that avoids evaporation steps. Initial biochemical analysis of a representative compound revealed that such GTP analogues can bind to Ras and might open up the possibility of developing small molecules that can act as deactivators of oncogenic Ras.