• DOI:10.1093/protein/gzu015
• Corpus ID: 17874917

Autolytic degradation of ocriplasmin: a complex mechanism unraveled by mutational analysis.

@article{Noppen2014AutolyticDO,
  title={Autolytic degradation of ocriplasmin: a complex mechanism unraveled by mutational analysis.},
  author={Bernard Noppen and Laetitia Fonteyn and Frans Aerts and Astrid de Vriese and Marc de Maeyer and François Le Floch and Philippe Barbeaux and Robert F. A. Zwaal and Marc Vanhove},
  journal={Protein engineering, design \& selection : PEDS},
  year={2014},
  volume={27 7},
  pages={
          215-23
        }
}

• B. Noppen, L. Fonteyn, +6 authors M. Vanhove
• Published 1 July 2014
• Biology
• Protein engineering, design & selection : PEDS

Ocriplasmin, a truncated form of plasmin, is commercialized in the USA and in Europe under the trade name Jetrea(®), and indicated for the treatment of symptomatic vitreomacular adhesion and vitreomacular traction including when associated with macular hole ≤400 µm, respectively. We have shown in a previous study that ocriplasmin undergoes autolytic degradation when injected in eye vitreous, which leads to its rapid inactivation. In order to investigate this process further, we have introduced in ocriplasmin a variety of amino acid substitutions within or in the immediate vicinity of the three major autolytic cleavage sites. We demonstrate here that autolytic inactivation of ocriplasmin is a sequential process where initial cleavage occurs primarily between residues 156 and 157. Reduction or even blocking of autolysis can be achieved by mutating a limited number of key residues. In this study, we also report the identification of a series of ocriplasmin variants with improved resistance to autolysis and unimpaired catalytic activity. Such variants represent useful tools for the exploration of therapeutic approaches aiming at non-surgical resolution of vitreomacular adhesion.