Provided correct acknowledgement is given. If you are an author contributing to an RSC publication, you do not need to request permission Please go to the Copyright Clearance Center request page. To request permission to reproduce material from this article in a commercial publication, Provided that the correct acknowledgement is given and it is not used for commercial purposes. This article in other publications, without requesting further permission from the RSC, Derda,Ĭreative Commons Attribution-NonCommercial 3.0 Unported Licence. Learning the structure–activity relationship (SAR) of the Wittig reaction from genetically-encoded substrates We anticipate that phage-displayed peptides and related mRNA or DNA-displayed substrates can be employed in a similar fashion to study the substrate scope and mechanisms of many other chemical reactions. Experimental measurement of reaction rates for 11 new sequences corroborated the predictions for 8 of them. This model can suggest new peptides never observed experimentally with ‘HIGH’ or ‘LOW’ reactivity. These classifiers achieved area under the ROC (receiver operating characteristic) curve (ROC AUC) of 81.2 ± 0.4 and 73.7 ± 0.8 (90–92% accuracy) in determining whether a sequence belonged to the top 5% or the bottom 5% in terms of its reactivity. By using these data, we trained two classifier models based on gradient boosted trees. We also collected deep-sequencing data to build structure–activity relationship (SAR) models that can predict the DC value of the Wittig reaction. Experimental measurement of reaction rates and density functional theory (DFT) computation of the transition state geometries corroborated this relationship. Peptide sequences with fast and slow reactivity highlighted the critical role of primary backbone amides (N–H) in accelerating the rate of the aqueous Wittig reaction. This “deep conversion” (DC) from deep sequencing correlates with rate constants measured by HPLC. ![]() Deep-sequencing of the biotinylated and input populations estimated the rate of conversion for each sequence. In this manuscript, we modified 160 000 N-terminal glyoxaldehyde peptides displayed on phage with the Wittig reaction by using a biotin labeled ylide under conditions that functionalize only 1% of the library population. The Wittig reaction can be used for late stage functionalization of proteins and peptides to ligate glycans, pharmacophores, and many other functionalities.
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