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Sickle Cell Treatment

Polymer poison
 
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Sickle cell anemia is a disease caused by a single mutation in the gene for hemoglobin. That single amino acid difference causes deoxygenated sickle hemoglobin to polymerize, and the big polymer chunks distort the red blood cells, causing them to sludge up and cause trouble.

The crucial area on hemoglobin must be very small if one amino acid difference causes it. I believe that with xray crystallography you could exactly describe the size and shape of that sticky site. I propose that a small molecule could be designed to fit exactly into that site. When sickle hemoglobin dexoygenates, the small molecule will glom onto the sticky mutant site before it can stick to another molecule of hemoglobin and start the polymerization going. When the hemolglobin picks up oxygen again, the site will disappear and the small molecule will be released.

The only problem with this treatment is that you would really need a lot of the small molecule - the dose of this would have to be high if there is to be some of this stuff in every red blood cell.

bungston, Jul 31 2004

Hemoglobin S polymerization http://www.physics....rrone_Research.html
I could not find any better description of polymerization that this. Too much fluid physics, not enough structure. [bungston, Oct 04 2004, last modified Oct 06 2004]

[link]






       Couldn't you just start clapping on "one" and "three"?
Ander, Jul 31 2004
  

       WHAT????
python, Jul 31 2004
  

       //caused by a single mutation in the gene for hemoglobin// I hope Bungco ensures that a multitude of RNA sites are not also involved before going to market....
ConsulFlaminicus, Jul 31 2004
  

       OK, from what I remember from bio 30, sickle cell anemia is a reccesive gene, and it's passed on from generation to generation and it's not a mutation. If you're Homozygous for the gene, you're pretty much screwed and are gonna have some serious heart problems. If you're lucky and are heterozygous for the gene, you're immune to malaria. But new blood cells only live for 120 days max so the dose would be very high. Otherwise it sounds interesting and might work, if you get the right structure of the "small molecule". good research +
swimr, Jul 31 2004
  

       This idea makes sense (I.E. contains no nonsense). That said, Such a molecule may or may not be possible to make. It seems like if you just use the short sequence of hemoglobin that is attacked by the other hemoglobin, and attach it to some small molecule, then you could attach that to the promoter for real hemoglobin and co-express them, then that might do it. Such molecules would put a "cap" on growing chains. Yeah, it's probably possible.   

       But, this isn't exactly going to be easy, and the one word in your idea "designed" will require years of innovation and work.   

       Great idea!
GutPunchLullabies, Jul 31 2004
  

       //Couldn't you just start clapping on "one" and "three"?// Cheap musician's Joke, [Ander], very cheap!.
You'll be putting a stone in the LEFT shoe in a minute.
gnomethang, Jul 31 2004
  

       I'm glad somebody got it.
Ander, Jul 31 2004
  

       I remember I once encounted an evolutionist who tried to explain to me that SCA was a positive mutation because of the immunity from malaria. Actually it sounds like the posibility of malaria is a better option.
tasman, Jul 31 2004
  

       Not really, because if you're heterozygous and are immune from malaria, you aren't affected by sickle cell anemia. But the downside is that your parents probably have it.
swimr, Aug 01 2004
  

       Now that the in crowd has had their chuckle, it is ok to explain the one and three joke? Something to do with syncopation?
bungston, Aug 01 2004
  

       For those of you who aren't familiar with the term "heterozygous," it means "having dissimilar alleles at corresponding chromosomal loci." Just thought I'd clear that up.
Ander, Aug 02 2004
  

       Actually, the physical shape of the deoxygenized hemoglobin, including the sticky spot, is fairly well-known thanks to current modeling software.   

       I like the idea, but the only downside is that it's very hard to get anything other than oxygen to enter erythrocytes. It may be best to find a way to introduce some sort of capsule into the marrow of a long bone (where the blood cells are produced), and to tie it to a compound which is readily taken in by healthy RBCs...and find some way to make the compound and your polymer poison separate once in the cell.   

       Some work to be done, but I like it.
shapu, Aug 02 2004
  
      
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