Talk:Aptamer/GA2

GA Review

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Reviewer: Mertbiol (talk · contribs) 17:45, 18 December 2022 (UTC)

I will take on this review. I do have some knowledge of DNA- and RNA-based aptamers, although I have never worked with them personally. I look forward to working with the nominator on this article. Best wishes Mertbiol (talk) 17:45, 18 December 2022 (UTC)

General comment

• There appears to be no quantitative discussion of the affinity with which an aptamer binds to a ligand. I think that a K_D range should be given in both the lead section and in the "Properties" section. (The term "affinity" is only used once in the main text!!)

Lead section

• I suggest combining the second and third sentences of the first paragraph to give: "They can bind strongly, with little or no off-target binding,^[1] and are sometimes classified as chemical antibodies."
• I suggest replacing "tasks" with "applications" in the (current) fourth sentence of the first paragraph.

Etymology

• I suggest mentioning that the first aptamer publication was in 1990.
• Please link Jack W. Szostak in the main body of the text.
• Per MOS:FOREIGNITALIC, please render "aptus" in italics as aptus.
• Please delete the second period (full stop) after "to fit."
• I suggest rephrasing "Aptamers are occasionally referred to as "chemical antibodies" or "antibody mimics"" to "Aptamers are occasionally classified as "chemical antibodies" or "antibody mimics".
• I suggest deleting "and sensitive" from the final sentence of this section.

History

• I am not sure if the history of directed evolution before SELEX should be covered in so much detail. I suggest rewriting first paragraph to give: "Since its first application in 1967, directed evolution methodologies have been used to develop biomolecules with new properties and functions. Early examples include the modification of the bacteriophage Qbeta replication system and the generation of ribozymes with modified cleavage activity."
• Please expand the acronym SELEX in the second paragraph, as this is the first mention of this term in the main body of the text.
• Please link Evgeny Nudler.
• I suggest changing "comprehensive proofs of" to "definitive evidence for"
• Please rephrase the final sentence of this section to read "This discovery added support to the RNA world hypothesis, a postulated stage in time in the origin of life on Earth."
• The single quotation marks around "RNA world hypothesis" should be removed.

Industry and Research Community

• I suggest moving this section to the bottom of the article. It may be worth rewriting this paragraph as an "External links" section.
• Bare URLs should be removed from this section.

Properties

(Just a start on this section - more to come)

• It is not clear what is meant by a "peptide aptamer". Is this an aptamer with an amino acid backbone or a nucleic acid-based aptamer with nucleotides modified with the addition of amino acids?
• Please replace "Typically, nucleic acid aptamers" with "Typically, DNA- and RNA-based aptamers".

Stopping here for now. I will provide additional feedback in due course. Best wishes Mertbiol (talk) 17:45, 18 December 2022 (UTC)

Affinity

Hi Mertbiol, I wanted to check on your request for "quantitative discussion of the affinity with which an aptamer binds to a ligand." The article on antibodies, which has attained "good article" status, does not discuss the KD range for antibodies. Of course, a KD range would be easy to add, but it sounds like you're interested in a longer discussion of aptamer affinity. If so, can you give some more specific suggestions for what you'd like such a discussion to cover? Thank you for your feedback! AllAmericanBreakfast (talk) 19:30, 18 December 2022 (UTC)

Hi @AllAmericanBreakfast: I have just had a quick check on the antibody article. You are correct in saying that there is no K_D range given, although "affinity" is mentioned 20 times in total. I think it would be a good idea to provide a typical K_D range for "useful" aptamers. Is there any difference between DNA-, RNA-, XNA- and peptide-based aptamers? At the moment, I don't think a long discussion is required - a single sentence in each of the lead section and in the properties section may be enough. Best wishes Mertbiol (talk) 19:48, 18 December 2022 (UTC)

Hi Mertbiol. The "useful" Kd range depends entirely on the specific application. For example, an in vivo biosensor needing to detect physiologically relevant levels of a specific protein will have its useful Kd determined by what the physiological levels are in the specific site, and depend also on the disease condition, inflammation, etc. By contrast, an aptamer used for affinity chromatography might have an entirely different "useful" range, potentially requiring significant affinity but much lower than that required to detect physiological levels. Other times, it might be specificity rather than affinity that is the key determinant of what makes an aptamer useful. Because the dynamic range of the aptamer depends on affinity, having an excessively high affinity can actually be bad for some applications. We could, however, give a range of affinities that have been reported in literature, just to show what has been achieved so far. AllAmericanBreakfast (talk) 20:15, 18 December 2022 (UTC)

Peptide aptamers

"It is not clear what is meant by a "peptide aptamer". Is this an aptamer with an amino acid backbone or a nucleic acid-based aptamer with nucleotides modified with the addition of amino acids?"

I believe the section covers this in "While most aptamers are based on nucleic acids, peptide aptamers are artificial proteins selected or engineered to bind specific target molecules." Let me know if that isn't clear enough. Thanks! AllAmericanBreakfast (talk) 19:41, 18 December 2022 (UTC)

Thanks @AllAmericanBreakfast: I can see the explanation lower down in the section now - I had not looked ahead. I think the "Peptide aptamers" definition is in the wrong place - it needs to be higher up when the term is first introduced. Best wishes Mertbiol (talk) 19:48, 18 December 2022 (UTC)