Date: Mar 11th 2025
Time: 2pm UK time other timezones
Place: https://ucl.zoom.us/j/91379419977
Recording: https://www.youtube.com/watch?v=oLksIgG90DA
Previous Meeting: #120
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) New data from Warwick on the contributed AZ compounds (including MICs, retests of IC50s at a lower concentration). Also, any updates on AZ compounds vs Mycobacterium? Need more samples? @LauraDS1
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 ) [further details on crystal refinement?]
iv) @Yuhang-CADD additional samples for complete the grid data of AZ compounds vs Eco (porin-deleted), Eco (WT), Pae (WT) as major priority (@AJLloyd105 How many mLs of 50mM solution needed in total?) The date of shipment depends on required sample amount, and the number of chemicals to be resynthesised due to data missing: see grid of data here)
(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
No new structures to add to the 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 Apr 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: Mar 11th 2025
Time: 2pm UK time other timezones
Place: https://ucl.zoom.us/j/91379419977
Recording: https://www.youtube.com/watch?v=oLksIgG90DA
Previous Meeting: #120
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) New data from Warwick on the contributed AZ compounds (including MICs, retests of IC50s at a lower concentration). Also, any updates on AZ compounds vs Mycobacterium? Need more samples? @LauraDS1
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 ) [further details on crystal refinement?]
iv) @Yuhang-CADD additional samples for complete the grid data of AZ compounds vs Eco (porin-deleted), Eco (WT), Pae (WT) as major priority (@AJLloyd105 How many mLs of 50mM solution needed in total?) The date of shipment depends on required sample amount, and the number of chemicals to be resynthesised due to data missing: see grid of data here)
(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
No new structures to add to the 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 Apr 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.