Abstract: In recent years, significant progress has been made regarding the site-specific introduction of modifications within peptides and proteins. Nevertheless, the development of efficient and versatile approaches is still required in order to further enlarge the scope of their applications. Chemical approaches can be a response to this need through the conception of fast and selective reactions enabling protein modification to proceed in dilute condition with high yield.

Recently, we have developed a chemoselective thioester-based ligation reaction which is highly efficient in highly dilute media (nanomolar concentration range) and which proceeds with rate constants up to 30 M^-1 s^-1. We now seek to extend this extremely efficient process called Fast-SEA ligation to the selective modification of large polypeptides and proteins. In this regard, we discussed how a latent and highly reactive oxalyl thioester precursor can be efficiently introduced as a pending functionality into a fully synthetic protein domain following a protection/late-stage deprotection strategy. This approach is illustrated with the production of a K48-ubiquitin conjugate.

Title of the article linked to the presentation : Incorporation of a Highly Reactive Oxalyl Thioester-Based Interacting Handle into Proteins

List of authors: Benjamin Grain, Rémi Desmet, Benoît Snella, Oleg Melnyk, and Vangelis Agouridas 

Citation: Organic Letters 2023, 25, 5117-5122.

Url: https://pubs.acs.org/doi/full/10.1021/acs.orglett.3c01846

Laboratory: Center for Infection and Immunity of Lille (CIIL)

City: Lille

Country: France