Date: May 13th 2025 & June 10th 2025
Time: 2pm UK time, 13th May 2025, other timezones
Place: https://ucl.zoom.us/j/91379419977
Recording: N/A
Previous Meeting: #122
Who can come?: Anyone. No need to say anything unless you'd like to.
Apologies: @Yuhang-CADD
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) New data from Warwick on the contributed AZ compounds (IC50s, MICs). Also, any updates on AZ compounds vs Mycobacterium? Need more samples?
iii) Update on crystallographic data of AZ compound 4 (WYH9 compound) in Pae MurD ligase (@scott) [how is the progress going, and whether need more samples?] & AZ5595 (WYH25 compound) in Pae MurC ligase (@LauraDS1 ) [actived site refined, suitable for docking, milestone progress!]
iv) @Yuhang-CADD has delivered the grid data of AZ compounds vs Eco (porin-deleted), Eco (WT), Pae (WT) as major priority **see grid of data here), waiting for Warwick team's IC50s and MICs as well as Crick team's ACC data to complete the paper.
v) @Yuhang-CADD designs for Multitargeting chapter & CC4CARB to announce.
(please add if you'd like to prioritise anything)
1) Multi-targeting Compounds from the Warwick/NEU Enamine Collection and Atomwise Compounds
2) Multi-targeting Elaborated Fragments from Diamond Fragment Screen
3) Variants of AZ Compounds
These will include guanidinium and pyridinium derivatives to try to combat efflux.
4) New Protein Structures
Laura's new full length Pae MurC with WYH78 (AZ13) in the ATP binding pocket, waiting for full refinement and deposit into PDB. PDB list.
5) De Novo Computational Modelling
@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)
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
8th July 2025
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.
Date: May 13th 2025 & June 10th 2025
Time: 2pm UK time, 13th May 2025, other timezones
Place: https://ucl.zoom.us/j/91379419977
Recording: N/A
Previous Meeting: #122
Who can come?: Anyone. No need to say anything unless you'd like to.
Apologies: @Yuhang-CADD
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) New data from Warwick on the contributed AZ compounds (IC50s, MICs). Also, any updates on AZ compounds vs Mycobacterium? Need more samples?
iii) Update on crystallographic data of AZ compound 4 (WYH9 compound) in Pae MurD ligase (@scott) [how is the progress going, and whether need more samples?] & AZ5595 (WYH25 compound) in Pae MurC ligase (@LauraDS1 ) [actived site refined, suitable for docking, milestone progress!]
iv) @Yuhang-CADD has delivered the grid data of AZ compounds vs Eco (porin-deleted), Eco (WT), Pae (WT) as major priority **see grid of data here), waiting for Warwick team's IC50s and MICs as well as Crick team's ACC data to complete the paper.
v) @Yuhang-CADD designs for Multitargeting chapter & CC4CARB to announce.
(please add if you'd like to prioritise anything)
1) Multi-targeting Compounds from the Warwick/NEU Enamine Collection and Atomwise Compounds
Update on crystallography trials at The University of Kansas (Scott Lovell, via @bartrum): Compound J06 (Z2010503124).
2) Multi-targeting Elaborated Fragments from Diamond Fragment Screen
3) Variants of AZ Compounds
These will include guanidinium and pyridinium derivatives to try to combat efflux.
4) New Protein Structures
Laura's new full length Pae MurC with WYH78 (AZ13) in the ATP binding pocket, waiting for full refinement and deposit into PDB. PDB list.
5) De Novo Computational Modelling
@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)
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
8th July 2025
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.