George Saunders

This report documents one of the most exciting observations we have ever made. Meticulously carried out by Marty and @GeorgeJSaunders this @J_A_C_S work shows how metastable 3-10 motif can be stabilized and enriched at high T. Should be a useful scaffold. pubs.acs.org/doi/abs/10.102…

Great to see this project out in its final form! We took a deep dive into the role of H-bonds in complex macrocyclic structures and found some interesting effects.

Proud to share this paper from my PhD studies on azetidine modified cyclic peptides! This was a very fun project to work on with some really cool outcomes and applications

Here is our study aimed at understanding cell penetration of oxadiazole-containing macrocycles. These are very peculiar molecules. Indebted to ⁦@ChemKritzer⁩ and his lab’s wonderful CAPA system. ⁦@Sean_SJ_Huh⁩ and Nefeli led the investigation. pubs.rsc.org/en/content/art…

In this study, expertly spearheaded by ⁦@DiegoBenDiaz⁩ (now at Merck #MerckChemistry) we investigate the role of attractive non-covalent interactions in peptide macrocyclization ⁦@JOC_OL⁩ pubs.acs.org/doi/10.1021/ac…

With @Sean_SJ_Huh (our recent PhD!) and @GeorgeJSaunders we deployed the rarely used Cornforth rearrangement to remove an atom from a macrocycle. This @angew_chem paper studies the interplay between reactivity and uncommon conformational states. doi.org/10.1002/anie.2…

Exciting news this Friday🎉 We’ve just published our second commentary piece by @andrei_yudin and @GeorgeJSaunders which provides additional viewpoints & contextualises earlier results from Alkane Kawamura, et al. You can read the Commentary here: rsc.li/3DCqqAT [1/2]

Many factors affect cellular permeability of macrocycles. Together with ⁦@GeorgeJSaunders⁩ we consider the effect of heterocycles in this paper that just came out. As luck would have it, George is giving a poster on this advance at #APS2022 today. onlinelibrary.wiley.com/doi/abs/10.100…

Tim McTiernan, @DiegoBenDiaz, @GeorgeJSaunders, Fiona Sprang and I describe MCMs (macrocycle conformational maps) that visualize conformational changes taking place in large ring systems. @genentech and @NSERC supported this study. 1/6

@dawber_robert @andrei_yudin Thanks for the question! Check out the solution structure of 6 (bottom left, red part of the arrow, or in Fig 4 of the pre-print article), its backbone conformation features two solvent exposed amide bonds which aren't favourable as it would cross the hydrophobic membrane.

@GeorgeJSaunders @andrei_yudin Nice poster George! Do you know why macrocycle 6 didn't 'fit the trend'? Is there something special about the structure of this one?

In this #RSCPoster I present work w/ @andrei_yudin towards new macrocyclic scaffolds that solve an unmet challenge in the development of bioactive cyclic peptides. We use heterocycles to discover membrane permeable conformations that are a platform for further development #RSCOrg

@Vy_Dong_Group @andrei_yudin As for bicycles, why not! The backbone conformation drives properties, and heterocycles force the backbone into distinctly unique conformational states compared to regular AA modifications. There are certainly other effects to discover with different heterocycles and combinations

@Vy_Dong_Group @andrei_yudin Great Q! We chose azoles because they are similar to the amide bonds that we are replacing and are easy to make from canonical AA's. One could certainly imagine a pyridine acting in a similar way to our azoles, with the N pointing into the macrocycle to H-bond with amide NH's.

@dawber_robert @RoySocChem @AJWilsonGroup @baylisslab That's interesting, thanks for the response. I wonder if there is a macrocycle out there that might be suitable for this PPI.

@GeorgeJSaunders @RoySocChem @AJWilsonGroup @baylisslab Thank you George, and great question! W77 is very important and makes up a large proportion of the buried surface area of the PPI. I haven't tried any pentapeptides, but I think the full helix at least is needed for strong binding. Peptide 18 was the best from a full staple scan

I’m delighted to share with you all my #RSCPoster for this year's @RoySocChem competition, showing my research within the @AJWilsonGroup and @baylisslab to try & develop inhibitors of the Aurora A/N-Myc protein-protein interaction! (Full poster & pitch below) #RSCChemBio (1/5)

@justyna_najczuk @RoySocChem @FurChem @pjczerw @IOC_PAS Interesting, thanks for the insight!

@GeorgeJSaunders @RoySocChem @FurChem @pjczerw @IOC_PAS Thank you! We provide reactions in planetary ball mill and horizontal ball mill and the second one is much louder. We have this mill in another room where we aren't working, because it's difficult to work with for a long time.

I am glad to share my work in this poster event, entitled "Grind, shake and mill: Reductive functionalization of fluoroacetamides". You will find picture of poster in comment. #RSCPoster, #RSCOrg, #mechanochemistry, @RoySocChem, @FurChem, @pjczerw, @IOC_PAS

Synthesis of α- and β-Carbolines by a Metalation/ Negishi Cross-Coupling/SNAr Reaction Sequence #RSCPosterLive #RSCOrg #RSCPoster

@JR_Chemistry Great poster. I wonder if you guys have ever tried this methodology with azetidines too?

Our contribution to the 2022 #RSCPoster! We developed a method to access amino-oxetanes through an alternative reaction of sulfonyl fluorides. Here we highlight the key features of our work. #RSCOrg #RSCPosterLive #RSCPoster2022

If you're interested in reading the full story, check out our ChemRxiv preprint here! doi.org/10.26434/chemr…