NMR-based discovery of phosphotyrosine mimetics that bind to the LCK SH2 domain

Bioorganic and Medicinal Chemistry Letters

Volumn 9, Issue 16, 1999, Pages 2403-2406

  Hajduk, Philip J ^a   Zhou, Ming Ming ^b   Fesik, Stephen W ^a  

^a ABBOTT LABORATORIES   (United States)

^b MOUNT SINAI SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

LIGAND; PHOSPHOTYROSINE; PROTEIN TYROSINE KINASE INHIBITOR; TYROSINE DERIVATIVE;

ARTICLE; BINDING AFFINITY; CONTROLLED STUDY; DRUG BINDING; DRUG BIOAVAILABILITY; DRUG STABILITY; NUCLEAR MAGNETIC RESONANCE;

MAGNETIC RESONANCE SPECTROSCOPY; MOLECULAR MIMICRY; MOLECULAR STRUCTURE; PHOSPHOTYROSINE; PROTEIN BINDING; PROTEIN-TYROSINE KINASES; SRC HOMOLOGY DOMAINS;

EID: 0033575666     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(99)00403-5     Document Type: Article

References (12)

1. Howe, L. R.; Weiss, A. TIBS 1995, 20, 59.
2. Brugge, J. S. Science 1993, 260, 918.
3. Eck, M. J.; Shoelson, S. E.; Harrison, S. C. Nature 1993, 362, 87.
4. Eck, M. J.; Atwell, S. K.; Shoelson, S. E.; Harrison, S. C. Nature 1994, 368, 764.
5. Ye, B.; Akamatsu, M.; Shoelson, S. E.; Wolf, G.; Giorgetti-Peraldi, S.; Yan, X.; Roller, P. P.; Burke, T. R., Jr. J. Med. Chem. 1995, 38, 4270.
6. Burke, T. R., Jr.; Smyth, M. S.; Otaka, A.; Nomizu, M.; Roller, P. P.; Wolf, G.; Case, R.; Shoelson, S. E. Biochemistry 1994, 33, 6490.
7. Tong, L.; Warren, T. C.; Lukas, S.; Schembri-King, J.; Betageri, R.; Proudfoot, J. R.; Jakes, S. J. Biol. Chem. 1998, 273, 20238.
8. Shuker, S. B.; Hajduk, P. J.; Meadows, R. P.; Fesik, S. W. Science 1996, 274, 1531.
9. Hajduk, P. J.; Meadows, R. P.; Fesik, S. W. Science 1997, 278, 497.
10. 2O, pH 7.2) in the presence and absence of added compound. Compounds were added as solutions in perdeuterated DMSO and were initially tested at 1.0 mM each in mixtures of 10. A Bruker sample changer was used on a Bruker AMX500 spectrometer. The total experimental time required to collect data on 3500 compounds was approximately 2 weeks. The compounds in the database were selected on the basis of size (average molecular weight = 213 Da) and molecular diversity. The molecules in the collection had different shapes (e.g., flat aromatic rings(s), puckered aliphatic rings(s), straight and branched chain aliphatics with single, double, or triple bonds) and diverse functional groups (e.g., carboxylic acids, esters, ethers, amines, aldehydes, ketones, and various heterocyclic rings).
11. 1H-NMR resonances and appeared soluble and stable.
12. Kay, L. E.; Keifer, P.; Saarinen, T. J. Am. Chem. Soc. 1992, 114, 10663.