Yuletide Mur Ligase Meeting December 2023

[mattodd]

Date: Dec 20th 2023
Time: 2pm UK time other timezones

Place: https://ucl.zoom.us/j/91379419977

Recording: https://youtu.be/HxW3dRa1MQE?si=BPLLbLV-KhxIJ9nk

Previous Meeting: #104
Who can come?: Anyone. No need to say anything unless you'd like to.

Apologies:

Decks: Please @opensourceantibiotics/murligase remember that if you share slides/info, to drag and drop those into a comment on this page, below. Very easy and saves @mattodd having to pester you.

Agenda:

Key things today are:

i) Multi-targeting compounds identified from Warwick and Atomwise collections. Updates on any new IC50 or crystallographic or microbiology data.

ii) Any data from Warwick on the contributed AZ compounds?

(please add if you'd like to prioritise anything)

1) Multi-targeting Compounds from the Warwick/NEU Enamine Collection and Atomwise Compounds

• @AJLloyd105 to update on further enzymatic screening of compounds from the Warwick Enamine Collection and Atomwise libraries, following discovery of the hits shown here.
• @LauraDS1 to update on any soaking and/or co-crystallisation experiments with these compounds, following (last update here.
  Update on crystallography trials at The University of Kansas (Scott Lovell, via @bartrum): Compound J06 (Z2010503124).
• @gfsfernandes to update on current research in design of improved binders vs TB murs.

2) Multi-targeting Elaborated Fragments from Diamond Fragment Screen

• @LauraDS1 to update on screening (inhibition, SPR, soak) of elaborated Diamond fragments sent by @edwintse in Compound to Warwick Inhibition Assay Jun 2022 #84.

3) Variants of AZ Compounds

• @Yuhang-CADD to ship fresh samples of AZ5595 and derivatives to Warwick in the new year, for analysis by @AJLloyd105. These will include guanidinium and pyridinium derivatives to try to combat efflux.

4) New Protein Structures

No new structures to add to the PDB list.

5) De Novo Computational Modelling

• @mattodd to organise what is known of the competition compounds and what is needed to write the work up for publication.

@Yuhang-CADD has paused synthesis of @jhjensen2's originally-suggested compounds (last update was here while the AZ derivatives are being made.

6) CC4CARB Proposal (#93)

• @mattodd and @eyermanncj to finalise current CC4CARB draft and submit. Help is needed from Warwick on commitment to compound evaluation.

7) Misc/AOB

Last time @AJLloyd105 reported on the evaluation, enzymatically, of "double-headed" compounds containing uridine and ATP binders: . These were found to be binders and will be investigated further (need to upload deck). @AJLloyd105 to update as appropriate.

8) Mothballs (if no actions then these need to be linked in wiki and closed)

@mattodd is in the process of converting old items to the wiki

Next Meeting

• @mattodd to arrange 2024 schedule and refresh invitee list.

L'esprit de l'escalier

If you'd like to follow up after the meeting, please comment below. You can also email, but please be clear if anything in the email should not be public domain - the default is always open.

[Yuhang-CADD]

Progress:

[mattodd]

Adrian Lloyd's presentation from today:

201223 OSA ATP Ap4A Up4A.pptx

[rhanson1046]

Thanks. It was an informative meeting today. Bob H

…

________________________________ From: Mat Todd ***@***.***> Sent: Wednesday, December 20, 2023 3:34 PM To: opensourceantibiotics/murligase ***@***.***> Cc: Hanson, Robert ***@***.***>; Team mention ***@***.***> Subject: Re: [opensourceantibiotics/murligase] Yuletide Mur Ligase Meeting December 2023 (Issue #106) Adrian Lloyd's presentation from today: 201223 OSA ATP Ap4A Up4A.pptx<https://github.com/opensourceantibiotics/murligase/files/13732769/201223.OSA.ATP.Ap4A.Up4A.pptx> — Reply to this email directly, view it on GitHub<#106 (comment)>, or unsubscribe<https://github.com/notifications/unsubscribe-auth/ANGWX5LP26SQZSZNFFKXBHLYKNKVFAVCNFSM6AAAAABAZQRMDCVHI2DSMVQWIX3LMV43OSLTON2WKQ3PNVWWK3TUHMYTQNRVGE3TGOBRHE>. You are receiving this because you are on a team that was mentioned.Message ID: ***@***.***>

[mattodd]

New paper on accumulation and drug design pinged to us by @gfsfernandes
https://pubs.acs.org/doi/10.1021/acs.jmedchem.3c01831