Stichting Sanquin Bloedvoorziening

Het Nederlands Kanker Instituut

New York University

Stichting Het Nederlands Kanker Instituut

Huib Ovaa

Antonius Nicolaas Maria Schumacher

Katerina Heran Darwin

Farid El Oualid

Nicolaas Sebastiaan Merkx

Rieuwert Hoppes

Boris Rodenko

Alessia Amore

Described are multimeric proteinaceous molecules comprising at least two members that bind each other via a region of noncovalent interaction, wherein a first of the members comprises a conditionally reactive group that, when activated, cleaves a covalent bond within the first member. Cleavage of the covalent bond results in a reduction in the binding strength with which the at least two members bind to each other via the region of noncovalent interaction. The reduction in the binding strength can result in the separation of the members under mild conditions.

Means and methods for breaking noncovalent binding interactions between molecules

Methods for making and using substrates of deamidase of prokaryotic ubiquitin-like protein (Dop) are described herein. More particularly, modified prokaryotic ubiquitin-like protein (Pup) and functional fragments thereof that serve as exemplary Dop substrates are described and encompassed herein. Screening methods to identify modulators of Dop and Pup activity and use of modulators identified thereby are also described. Methods of using modulators that are identified as inhibitors of Dop and Pup activity for treating diseases/conditions associated with(Mtb) infection, such as tuberculosis and leprosy, are also envisioned.

Modified prokaryotic ubiquitin-like protein and methods of use thereof

The present invention concerns multimeric proteinaceous molecules comprising at least two members that bind each other via a region of noncovalent interaction, wherein a first of the members comprises a conditionally reactive group that, when activated, cleaves a covalent bond within the first member. Cleavage of the covalent bond results in a reduction in the binding strength with which the at least two members bind to each other via the region of noncovalent interaction. The reduction in the binding strength can result in the separation of the members under mild conditions.

The present invention concerns new thiolysine and selenolysine compounds that can be used as building blocks for peptides and proteins, providing ligation handles for site- and chemoselective modification of said peptides and proteins. In particular, the invention provides. In particular, the invention provides (the use of) the compounds 5-thiolysine (also referred to as &#x3b4;-thiolysine); 4-thiolysine (also referred to as &#x3b3;-thiolysine); 5-selenolysine (also referred to as &#x3b4;-selenolysine) and 4-selenolysine (also referred to as &#x3b3;-selenolysine). The positioning of the thiol or selenol group at the respective carbon atom allows for a very efficient intramolecular transfer reaction to take place after conjugation with a selected ligand, and the thiol or selenol group may subsequently be removed using reported procedures, thereby restoring the native lysine structure, or be used as an additional conjugation handle. The methodology is fast and gives well-defined material.

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Amsterdam, Netherlands

Huib Ovaa