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Response to TxDemChem (Reply #4)

Thu Aug 31, 2017, 09:14 PM

5. You know, for most of my life I've been a peptide/protein kind of guy, at least so far as...

...medicinal chemistry goes, since for much of my career I've worked with peptidomimetics, which actually has bearing on the OP in this thread.

You get to thinking that that is where all the action is.

I while back I ran across a wonderful text, called The Sugar Code because I was looking into the issue of glycans as post translational modifications of, um, proteins and I was struck by the depth and importance of glycomics about which I'd actually thought very little.

Like most of the books you actually end of reading, it has a captivating opening:

Teaching the biochemistry of carbohydrates is not simply an exercise in terminology. It has much more to offer than commonly touched upon in basic courses, if we deliberately pay attention to the far-reaching potential of sugars beyond energy metabolism and cell wall stability. In fact, then there is no reason why complex carbohydrates should shy at competition with nucleic acids and proteins for the top spot in high-density biocoding. On the contrary, sugars have ideal properties for this purpose, as will be concluded at the end of this chapter. In this sense, an obvious explanation why research in glycosciences (structural and functional glycomics and lectinomics) has lagged behind the fields of genomics and proteomics, also in the public eye, is 'that glycoconjugates are much more complex, variegated, and difficult to study than proteins and nucleic acids' [1]. What is a boon for decorating cell surfaces with a maximum number of molecular messages at the same time has been and still is a demanding challenge for analytical and synthetic chemistry (please see Chapters 3-5 for details on how to address it properly).

Put another way, people don't pay attention to the roles of sugars because sugar chemistry is hard.

You just have to go forward in a book like that.

I confess, I wasn't much interested in nucleic acid biochemistry either, until at least I attended a "Science on Saturday" lecture at the Princeton Plasma Physics lab by Shirley Tilghman, the former President of Princeton University, who got tired of all that administrator stuff and went back to the lab.

The lecture is on line: PPPL Science on Saturday lecture: The Wild and Wacky World of Epigenetics

A little while later I found myself begging a technical guy at a major mass spec company to offer software to dig post translational modifications of nucleic acids, some equivalent of say, Sciex's Protein Pilot.

(He personally agreed with me, but it ain't happened yet.)

It may happen that nucleic acid chemistry will end up being as important in therapeutics as proteins and the related ADC's (antibody drug conjugates) are now. There are certainly some companies betting on that. I've recently had the pleasure of working with some folks on revivified gene therapy programs. They're powerfully intriguing. It would be wonderful if they proved viable. Lives would be saved.

Nucleic acid biochemistry, in which I am in no way an expert, I believe, must be fascinating. If I don't run out of time in my life, I'd love to understand it more deeply. I'm coming to understand, if not on a profound level of deep knowledge, how beautiful it is.

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