4 ms·

I might be missing something but I don't see how adding DNA nucleotides can lead to novel proteins. You have more letters to potentially map to amino acids, but

I might be missing something but I don't see how adding DNA nucleotides can lead to novel proteins. You have more letters to potentially map to amino acids, but unless you've also expanded your set of amino acids, how does this lead to new proteins? And did they also design new t-RNA's (the things that maps RNA to amino acid)?

natechols 8y ago
They have indeed expanded their set of amino acids. I assume they must have added tRNAs as well but the article didn't go into this detail.
- dnautics 8y ago
  Romesberg got mRNAs up about 3-4 years ago? I presume the tRNAs are made from processed DNA, not by adding them (adding tRNAs exogenously to bacteria would be tough, and not economical at all).
harshreality 8y ago
My interpretation, though it doesn't go into it in the article, is that ribosomes are capable of translating abnormal tRNA bases to abnormal amino acids; they just normally don't do it because there aren't tRNA strands floating around with abnormal bases on them. They happened to find an abnormal DNA/RNA base pair, and it happened to be mapped by the ribosome to a PEG amino acid (I think the implication is NH2-PEG-COOH?), and relized if they swapped out an existing amino acid in IL-2 with that PEG-based amino acid, the protein would be less toxic? Another thought: it might not be strictly a RNA-base-X maps to amino-acid-x type of operation; RNA-base-X might map to either amino-acid-x or amino-acid-y based on concentrations of AA-x and AA-y, or even based on neighborhood structure of the protein that's under construction, and they just got lucky with IL-2 or they figured they could put tons of PEG into a cell and get most IL-2 produced with that PEG-based amino acid?
dnautics 8y ago
Floyd was Pete Schultz' postdoc, one of Pete Schultz' claims to fame is really nailing down unnatural AA stuff. IIRC, the peg UAA has been around for quite a while (at least a decade).
gweinberg 8y ago
I think there are theoretically an infinite number of amino acids out there. An amino acid has a backbone structure and two side chains, but in principle the side chains can be anything.

natechols 8y ago

They have indeed expanded their set of amino acids. I assume they must have added tRNAs as well but the article didn't go into this detail.

dnautics 8y ago
Romesberg got mRNAs up about 3-4 years ago? I presume the tRNAs are made from processed DNA, not by adding them (adding tRNAs exogenously to bacteria would be tough, and not economical at all).

harshreality 8y ago

My interpretation, though it doesn't go into it in the article, is that ribosomes are capable of translating abnormal tRNA bases to abnormal amino acids; they just normally don't do it because there aren't tRNA strands floating around with abnormal bases on them. They happened to find an abnormal DNA/RNA base pair, and it happened to be mapped by the ribosome to a PEG amino acid (I think the implication is NH2-PEG-COOH?), and relized if they swapped out an existing amino acid in IL-2 with that PEG-based amino acid, the protein would be less toxic? Another thought: it might not be strictly a RNA-base-X maps to amino-acid-x type of operation; RNA-base-X might map to either amino-acid-x or amino-acid-y based on concentrations of AA-x and AA-y, or even based on neighborhood structure of the protein that's under construction, and they just got lucky with IL-2 or they figured they could put tons of PEG into a cell and get most IL-2 produced with that PEG-based amino acid?

dnautics 8y ago

Floyd was Pete Schultz' postdoc, one of Pete Schultz' claims to fame is really nailing down unnatural AA stuff. IIRC, the peg UAA has been around for quite a while (at least a decade).

gweinberg 8y ago

I think there are theoretically an infinite number of amino acids out there. An amino acid has a backbone structure and two side chains, but in principle the side chains can be anything.