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Koenig Polyanion Print E-mail
    This is a copy of the letter posted by Prof. Marco Colombini to MITOCHONDRIA mail list in 2007. It might be helpful to someone looking for a VDAC inhibitor.

 Professor Marco Colombini    on   Koenig Polyanion "VDAC inhibitor":

    Many years ago I received Koenig's Polyanion from Tamas Koenig. It was a gift that I've shared with many people over the years. I've always warned people that this material is NOT specific for VDAC. It has many targets, as Dr. Koenig showed in his experiments. However it is a rather potent blocker of VDAC. More recently, my lab has published that a phosphorothioate oligonucleotide is a potent and much more specific inhibitor of VDAC when added to isolated mitochondria. The compound called G3139 is a proprietary product of GENTA Inc. and being considered as an anti-cancer drug. G3139 has effects other than action on VDAC but a random sequence of the same length works just as well without known side effects. At levels of 1 micromolar or less, we find only inhibition of VDAC (no effect on respiration, ANT, RCR). Clearly we know that the specificity of inhibitors decays with time but, at this point, this is the most specific inhibitor of VDAC (in my opinion). It is commercially available. The "randomer" is available from Trilink Industries**. They  don't say what the molecule is for, even though the only reason they are carrying it is that Cy Stein and I have urged them to carry it as a VDAC inhibitor. The catalog number is: 0-30030-50 A random sequence that is the same size and charge but has just phosphodiester linkages (as opposed to phosphorothioate) is also available as a control. It has no effect on VDAC at 10 micromolar concentration. Of course, being a polyanion, at high concentrations it will have the typical polyanion effect. The catalog number for the control compound is 0-30040-50 See the publications on my web site for more details; see especially Table 2 in: Tan, W., Lai, J.C., Miller. P., Stein, C.A., and Colombini, M. 2007. Phosphorothioate Oligonucleotides Reduce Mitochondrial Outer Membrane Permeability to ADP. American Journal of Physiology 292: C1388-C1397. (full text)

P.S.  If I may set the record straight, aluminum hydroxide and the trihydroxides of gallium and indium inhibit the voltage-dependent closure of VDAC. However, these are insoluble at neutral pH but can be generated in a metastable state by adding the chloride salts to a well-buffered solution. It is only in this state that they inhibit VDAC closure.

Best, Marco Colombini

**  I was not able to locate this company. A closest name match I found is "TriLink Biotechnologies" (web site) but I did not find this compound in their catalog - Anatoly Starkov.

Last Updated ( Tuesday, 04 December 2007 )
 

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