tag:blogger.com,1999:blog-2909827059962062852.post4283693449997310632..comments2024-03-26T17:10:36.305+00:00Comments on Molecular Design: Ligand deconstructionPeter Kennyhttp://www.blogger.com/profile/12180360326821860667noreply@blogger.comBlogger2125tag:blogger.com,1999:blog-2909827059962062852.post-25410046817807332422012-09-22T23:21:33.181+01:002012-09-22T23:21:33.181+01:00Thanks, Dan, for flagging up the pH of 7.0. I was...Thanks, Dan, for flagging up the pH of 7.0. I was pretty sure it would be there and thought that I'd checked properly by searching the PDF for pH. Apparently not though and I may even post an 'ich bin dummkopf' to atone for my sins!<br /><br />Back to the deconstuction. The main reason for the post was highlight some of the issues raised by deconstruction. Hopefully it'll get folk thinking a bit more. When I was at AZ we used to talk about 'prototypical reaction products' in the context of libary design and this is another way to think about deconstruction.Peter Kennyhttps://www.blogger.com/profile/12180360326821860667noreply@blogger.comtag:blogger.com,1999:blog-2909827059962062852.post-41729517233228194712012-09-21T16:31:19.802+01:002012-09-21T16:31:19.802+01:00Nice analysis – this paper was also highlighted on...Nice analysis – this paper was also highlighted on Practical Fragments:<br /><br />http://practicalfragments.blogspot.com/2010/04/hot-spots-for-fragments.html<br /><br />Note that they did provide the pH for their NMR experiments (7.0).<br /><br />You raise some important points about the limits of ligand deconstruction. However, I do think it’s important to note that they tested 22 different fragments, some of which had less perturbing disconnections than the ones shown here.<br /><br />I think one of the most interesting findings in this paper is the fact that while many of the fragments bind to the protein, some of them do so at a different site (“site 1”) than in the fully elaborated molecules. In fact, one of the fragments that binds to site 1 in this study binds to site 2 in a previous study, because of the presence of another fragment binding in site 1 in that experiment.Dan Erlansonhttps://www.blogger.com/profile/07927082337051189270noreply@blogger.com