ADC, Antibody Drug Conjugate, bispecific molecules, Protein PEGylation, Protein imaging

Almac’s proprietary ligation technology

The recombinant protein of interest is expressed as an N-terminal intein fusion protein. The properties of the intein domain are such that it induces an N to S acyl shift at this protein-intein junction to form the thioester intermediate.

This thioester intermediate is chemically cleaved under aqueous buffered conditions using hydrazine or dioxyamine to liberate the corresponding C-terminal hydrazide and aminoxy derivatives of the target protein.

The C-terminal derivatives chemoselectively react with ketone or aldehyde containing moieties (benzaldehyde PEG shown here) resulting in site specific C-terminal modification of the recombinant protein via stabilized hydrazone or oxime linkage.

Click on image to enlarge

Key advantages of our technology

  • Targeted, site specific ligation at the C-terminus – allows total control over the ligation process
  • Retained biological activity – has the potential to improve upon the native protein i.e. by extending half life while maintaining the activity
  • Robust, high yielding conjugation technology
  • Mono conjugated species – COGs savings and lower dosing potential
  • Conjugate equivalents ratio – low ratio equates to savings on COGs
  • Compatible with disulphide-bond containing proteins
  • Applicable to a wide range of labels and modifications
  • Single modification site means homogeneous products produced 
Flash replacement image