Open TomkUCL opened 1 year ago
Today's monthly meeting agenda will include the following:
Setting up the SPR assay (ordering of chips, reference compounds (ADP, ATP-analogues, Joe Newman fragments, gathering chip-binding and protein regeneration protocols from Levon using human helicases as a reference); see here: https://github.com/StructuralGenomicsConsortium/CNP4-Nsp13-C-terminus-B/issues/25
Discussion of synthetic routes; https://github.com/StructuralGenomicsConsortium/CNP4-Nsp13-C-terminus-B/issues/27
Update on the gram-scale synthesis of a key intermediate of generative compounds list: TK-41-3: Preparation of ethyl 2-(5-fluoropyridin-2-yl)acetate. https://uk-mynotebook.labarchives.com/share/Thomas%2520Knight/MTI0LjgwMDAwMDAwMDAwMDAxfDEwNDQxLzk2L1RyZWVOb2RlLzM1ODI4MzU2Mzl8MzE2Ljc5OTk5OTk5OTk5OTk1
Cool. Could you please post the meeting link here for newbies and tweet out pinging me and using #sgc-ocn? If someone could provide a short update on heli-hub in the meeting, that'd be great.
Cool. Could you please post the meeting link here for newbies and tweet out pinging me and using #sgc-ocn? If someone could provide a short update on heli-hub in the meeting, that'd be great.
To join today's recorded Zoom meeting, follow this link: https://ucl.zoom.us/j/97172937586
Hi all,
The video recording from today's nsp13 meeting can be found here: https://ucl.zoom.us/rec/play/8-4QrgvPlmshTWaQEYCIymChyqdh1sbSbcvZZ52VnTeHWeyNB5-4eHGOJsWSubh-11vaHwm4lkVGge3L.T_bZYKBJgpmj4Kga Passcode: xF7^L@zW
In this meeting we mentioned the possibility of using other Nsp13 binding proteins as a control to indicate the SPR assay works. Otherwise: ADP and a non-hydrolysable ATP analog. @SumeraMalik123 used a peptide control; has just published a paper on some Nsp13 binders (https://pubs.acs.org/doi/10.1021/acsinfecdis.2c00165).
@jamesday100 thinks our compounds appear to be good-looking solubility wise, which helps for SPR.
There is a push in Toronto for some ASMS experiments, including Nsp13. We should keep an eye on this (@toluene44 is involved).
Vanderbilt attendees (Samantha Grimes, Jordan Anderson-Daniels) - doing mutagenesis. Could potentially do our site? They mentioned that, interestingly, blocking cleavage between Nsp13 and 14 maintains live virus. Implies the RTC works even without fully cleaved components. Not so for Nsp12 and 13, however: if they remain conjoined, virus is screwed.
Please see below for details of today's Zoom meeting discussing updates around the SARS-CoV-2 nsp13 helicase fragment-based drug discovery project for site 3.