This is the last Monday's Molecule for 2008. There will be a short Christmas break. Monday's Molecule will return on January 5th. As part of the Christmas celebrations, this week's molecule is a gift. Your task is to identify this molecule and give it a biochemically accurate name (the IUPAC name would be perfect). The Nobel Laureate should be obvious once you identify the molecule.
The first one to correctly identify the molecule and name the Nobel Laureate, wins a free lunch at the Faculty Club. Previous winners are ineligible for one month from the time they first collected the prize.
There are four ineligible candidates for this week's reward: Ms. Sandwalk from Mississauga, Ontario, Canada, Alex Ling of the University of Toronto, Timothy Evans of the University of Pennsylvania, and John Bothwell of the Marine Biological Association of the UK in Plymouth, UK. John, Dale and Ms. Sandwalk have offered to donate the free lunch to a deserving undergraduate so the next two undergraduates to win and collect a free lunch can also invite a friend. Alex got the first one.
THEME:
Nobel Laureates
Send your guess to Sandwalk (sandwalk (at) bioinfo.med.utoronto.ca) and I'll pick the first email message that correctly identifies the "molecule" and names the Nobel Laureate(s). Note that I'm not going to repeat Nobel Laureate(s) so you might want to check the list of previous Sandwalk postings by clicking on the link in the theme box.
Correct responses will be posted tomorrow. I reserve the right to select multiple winners if several people get it right.
UPDATE: The molecule is 2&prime,3′-dideoxycytidine 5′-monophosphate. This molecule differs from the normal cellular version of deoxycytidine because it is missing a second hydroxyl group at the 3′ position on the sugar. The triphosphate version of this molecule is a substrate for DNA polymerase and it will be incorporated into a growing DNA chain. However, once it is incorporated, the polymerization reaction stops because the 3′ hydroxyl group is essential for addition of the next nucleotide.
Dideoxynucleotides are used in the chain termination method of DNA sequencing developed by Frederick Sanger. Sanger received his second Nobel Prize in 1980 for developing this method, which remains the most popular method of DNA sequencing.
I was surprised that only a few people responded and even more surprised that some of the regulars didn't give a correct name for this molecule. There is no winner this week because I am being strict about nomenclature. If you didn't specify where the phosphate is attached (5′) or you used "cytosine" instead of "cytidine," then you don't get a free lunch! (Cytosine is the base, cytidine is the nucleoside.)
13 comments :
God, you're a nomenclature snob! Alright, alright, full IUPAC it is next time...
The phosphate thing is RIDICULOUS! Dideoxycytidine monophosphate can have phosphate only in one position!
Yeah, DK might be right. "Dideoxycytidine monophosphate" could have its deoxy bits at 2', 3', or 5', so you could have, say, "2',5'-dideoxy" and the PO4 on 3'. But if you specify "2',3'-dideoxy", then that only leaves the 5' site available for esterification. I also have a suspicion that the IUPAC convention for nucleoside phosphates assumes a 5' PO4 unless otherwise stated, but I couldn't be bothered to check right now.
If you ask me, the whole thing smacks of someone who's realized they're a bit short of cash in the run-up to Christmas and wants to save themselves the cost of a faculty lunch...
AND...
...I notice that the first figure in your Sanger post doesn't give the 5' position for the triphosphate. Which dubious textbook does that come from?
Dideoxycytidine monophosphate" could have its deoxy bits at 2', 3', or 5', so you could have, say, "2',5'-dideoxy" and the PO4 on 3'. But if you specify "2',3'-dideoxy", then that only leaves the 5' site available for esterification
Yep. That's why my email to Larry had the name spelled as
"2',3' dideoxycytidine monophosphate".
DK says,
The phosphate thing is RIDICULOUS! Dideoxycytidine monophosphate can have phosphate only in one position!
Good point! You're right, of course, as long as you confine the possibilities to the common nucleotides.
However, it is possible to have 1′ and 4′ phosphates, isn't it? You could avoid that possibility by specifying α-D-2′,3′- dideoxyribofuranose.
Nobody did that.
However, it is possible to have 1′ and 4′ phosphates, isn't it?
I don't think so. Two reasons:
1) if you stick to *cytidine* (which is correct), then no, 1' and 4' phosphates are not possible.
2) Alternatively, you can imagine carbon-phosphorus bond on 1' and 4' but that would not be *phosphate*.
Again, I think I'm going with DK on this; if you specify cytidine, then there are only 3 available -OH groups for esterification (2',3',5'). If you say what's happened to two of them (2',3'-dideoxy) then that leaves only one site for the PO4.
As DK says, yes, you could have a 1' or 4' C-O-P bond, but then your starting molecule wouldn't have been cytidine; it'd have been some weird hydroxyribofuranose.
Finally, you asked for "the IUPAC name" and I'm not sure that there is any such thing. IUPAC "names" aim to provide the minimum description to unambiguously identify a molecule and there are conventions in there to reduce redundant information of the sort which I think "5'-monophosphate" would be.
BUT...
...I've been wrong before, so may well be wrong about that last point; I'll try to check IUPAC today, if I get the time.
You still write a great blog, 'though, and Merry Christmas!
DK says,
1) if you stick to *cytidine* (which is correct), then no, 1' and 4' phosphates are not possible.
Why not? The furanose configuration exists in equilibrium with the open chain form of ribose (or dideoxyribose).
During the time when the sugar is in the open chain form does the molecule assume another name? What is it?
This is a fun conversation but let's not lose sight of the main point. I agree with you that leaving out the 5′ isn't as egregious as I first thought. It was dumb of me not to realize that the 3′-monophosphate couldn't exist.
On the other hand, I really was expecting a more detailed name for the molecule. It's not deoxycytidine, so the proper way to describe the molecule that's shown is to describe the sugar and its configuration and add cytosine.
Why not? The furanose configuration exists in equilibrium with the open chain form of ribose (or dideoxyribose)
Because once you phosphorylate linear form (which I don't think exists anyway when modified with cytosine on C1), it can never go back to a ring form - and this means that you no longer have cytidine!
so the proper way to describe the molecule that's shown is to describe the sugar and its configuration and add cytosine
Disagree! Next you probably will be telling that "DNA" is not a proper name either. We been there already. The proper name is the one that is used and understood universally. That is, the proper name for ATP is "ATP" or, infrequently, adenosine triphosphate but not whatever IUPAC has dreamed up. Likewise, the proper name for ddCMP is just that or, in rare cases, dideoxy CMP. Everyhting else only applies to special cases and needs, e.g. when specifically dealing with weird stuff.
DK says,
Because once you phosphorylate linear form (which I don't think exists anyway when modified with cytosine on C1), it can never go back to a ring form - and this means that you no longer have cytidine!
I don't understand why you say this. The furanose configuration of the sugar is just one of many possible configurations and conformations. It doesn't change the fact that the molecule is still called cytidine (or cytidine 4′-monophoshate, to be precise).
I'm sure you're aware of the fact that the base, cytosine, can also exist in different configurations. The two main tautomeric forms are the amino and keto forms. Do you think that one of them is legitimate cytosine and the other should be called something else? :-)
Disagree! Next you probably will be telling that "DNA" is not a proper name either.
The term "DNA" is sufficient to describe the basic chemical composition of the molecule under most circumstances. However, if I were to show you an image of a short stretch of Z-DNA it would not be sufficient to simply call this "DNA." In that case, if I specifically asked for a complete description on an exam, you would have to tell me what form was being depicted. Right?
Same with cytidine. I happened to show you an image of the molecule with the base in the amino tautomeric form, with cytosine in the anti conformation, and the sugar in the β furanose configuration.
I don't know why you are making such a fuss about this unless you think that the word "cytidine" is restricted to one particular configuration/conformation. Is that what you think?
We been there already. The proper name is the one that is used and understood universally. That is, the proper name for ATP is "ATP" or, infrequently, adenosine triphosphate but not whatever IUPAC has dreamed up.
IUPAC agrees with you. The term "ATP" can be used as a shorthand version of adenosine 5′-triphosphate. In most cases that's good enough but if I were to show you several different configurations/conformations of ATP on an exam and ask you to identify them by name, you wouldn't get very many marks if you just called them all ATP.
Likewise, the proper name for ddCMP is just that or, in rare cases, dideoxy CMP.
I think that in all cases ddCMP, would be understood to mean 2′, 3′-dideoxycytidine 5′-monophosphate. That's not what we're discussing.
I have already admitted that the point of attachment of the phosphate group is less important that I first realized because I stupidly didn't realize that the 3′-monophosphate is impossible.
What I was referring to when I asked for a "biochemically accurate" name was to specify the more accurate name, 2′, 3′-dideoxycytidine 5′-monophosphate, and the particular version that was shown in the figure.
Everyhting else only applies to special cases and needs, e.g. when specifically dealing with weird stuff.
No. There's also the distinction between different configurations and conformations of the same molecule. When you are asked to specify this you must demonstrate that you know the difference.
it can never go back to a ring form - and this means that you no longer have cytidine!
I don't understand why you say this.[snip]
You are being silly. I give up. Using your logic, L- and D-aminoacid is the same thing because there is actually an equilibrium between two forms.
So much for "biochemically accurate"...
DK says,
You are being silly. I give up. Using your logic, L- and D-aminoacid is the same thing because there is actually an equilibrium between two forms.
That's not what I'm saying at all.
I'm saying that if I showed you the structure of D-serine and asked you to give me a correct biochemical name then "serine" would not be sufficient.
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