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US 9,850,469 B2Granted
Methods of stapling and unstapling peptides and proteins
AssigneeThe Trustees of the University of Pennsylvania
InventorsAmos B. Smith, III, Stephen Brown
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Abstract
The present disclosure pertains to the field peptide stapling and/or macrocyclization, where a structural motif is used to improve the properties of amino acid sequences (e.g. protease resistance, cellular penetration, biological activity). Also within the scope of the disclosure are methods for unstapling the S,S-tetrazine-containing amino acid sequence. The disclosure is also directed to methods for the reductive removal of thiocyanates from an amino acid sequence with cysteine to recycle back to the native amino acid sequence.
Claims15
A process comprising:
- preparing a phase-transfer reaction medium comprising
- an aqueous solution of an unprotected amino acid sequence comprising two proximal cysteine residues or two homocysteine residues;
- and
- an organic solution of a di-halo-tetrazine;
- contacting the aqueous solution with the organic solution for a time sufficient to form an S,S-tetrazine moiety;
- irradiating the S,S-tetrazine moiety with light to form an amino acid sequence comprising two proximal thiocyanate moieties;
- and
- contacting the amino acid sequence comprising two proximal thiocyanate moieties with cysteine for a time sufficient to produce the amino acid sequence comprising two proximal cysteine residues or the amino acid sequence comprising two proximal homocysteine residues;
- wherein the proximal cysteine residues, the proximal homocysteine residues, and the proximal thiocyanate moieties are separated by 0 to 35 amino acid residues.
6 more elements
Dependencies are inferred from the claim text.