KinasePro

Kinase Chemistry – Just a year and a half behind the times.

PDB Update

Posted by kinasepro on September 26, 2007

VEGF: Amgen: J Med Chem; 2QU5; 2QU6 (C817A, V916T, E990V)

O=C(C1=NC=CC(OC2=CC=C3C(N=C(NC4=CC=C(Cl)C(C(F)(F)F)=C4)N3)=C2)=C1)NC

FGFR2: NYU: “A Molecular Brake” Mol. Cell
WT 2PSQ
WT 2PVF w/substrate
K659N 2PVY
N549H 2PWL
E565G 2PY3
N549T 2PZ5
K526E 2PZP
K641R 2PZR
E565A 2Q0B

CK2: 2OXD,2OXX,2OXY, ChemBiochem

EphA5: 2R2P (SGC)

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10 Responses to “PDB Update”

  1. In your header bar you have an image of 2OFU from Amgen. Is there any special significance, or is it just something that you regarded as being worthy?

  2. *What* exactly is that F bonding with? F is a very poor H-bonder. But check the latest Science issue for a review on F in pharmaceuticals.

  3. I can’t say I understand it very well, but maybe it’s a halogen bonding interaction…
    http://pubs.acs.org/cgi-bin/abstract.cgi/achre4/2005/38/i05/abs/ar0400995.html

  4. That’s the interesting dichotomy. Br and Cl will bond to O in the carbonyl while F bonds to the C.

  5. rosko said

    *What* exactly is that F bonding with?

    It looks more like that dotted line is coming from that glutamate in front of the CF3 group and ending on the lysine, therefore indicating an ionic interaction. A quick look at the 3D structure confirms this suspicion. I agree it looks ambiguous in 2D, though.

  6. Fluorine is indeed a weak hydrogen bond acceptor and each these will be further weakened by the presence of two more of their kind. Other halogens can indeed interact with hydrogen bond acceptors and the interaction gets stronger as halogen becomes heavier or the the electron pull of whatever the halogen increases. I’ve not taken a close look a the structure but would guess that the CF3 interacts with protein thru hydrophobic interactions. Note that fluorines on carbon next to anionic groups (e.g. CF2PO3– in PTP ligands) draw negative charge towards them and can interact with HB donors in the protein. Returning to 2qu5, note how the pyridine wins its battle with benzimiadazole for the linking oxygen lone pair.

  7. kinasepro said

    TM- I made the header back when I decided to make a new header every week… Sadly that paradigm lasted about two weeks 😦

    And yah, the benzimidazole is suppsed to be a Nexavar styled urea isostere… Merck DE has filed application after application on the motif, and while I’m not sure who actually owns these compounds – the ones I’ve seen like this haven’t worked out all that great.

  8. milkshake said

    Your header is perfectly fine – and please keep up the work.

    The Thursday patent list: is there any way I can get it from you, even for a subscription? We won’t need a complete list, just selected few kinases that we work on.

    Thanks. Milkshake

  9. kinasepro said

    sup Milks… See above.

  10. Murray said

    Though not F specific, an interesting review of halogen bonding in PKs.

    http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=17692024&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

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