Mechanism of inactivation of ocriplasmin in porcine vitreous
| Autor: | Bernard Noppen, Marc D. de Smet, Rita Derua, Marc Vanhove, F. Aerts, Etienne Waelkens, Laetitia Fonteyn |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Scaffold protein
Autolysis (biology) Posterior vitreous detachment Arginine Plasmin Swine Molecular Sequence Data Biophysics Buffers Biochemistry law.invention chemistry.chemical_compound law Local or partial unfolding medicine Animals Symptomatic vitreomacular adhesion Amino Acid Sequence Disulfides Fibrinolysin Protein Unfolding Protein Stability Organic Chemistry Ocriplasmin Hydrogen-Ion Concentration medicine.disease Vitreomacular adhesion eye diseases Peptide Fragments Vitreous Body Kinetics chemistry Proteolysis Recombinant DNA sense organs Autolysis medicine.drug |
| Zdroj: | Biophysical chemistry. |
| ISSN: | 1873-4200 |
| Popis: | Ocriplasmin, a 249-amino acid recombinant C-terminal fragment of human plasmin, has the potential to degrade, within the eye, the protein scaffold that links the vitreous to the retina. This may be beneficial to the treatment of a number of important ophthalmic indications, such as symptomatic vitreomacular adhesion. We demonstrate here that ocriplasmin used at therapeutically-relevant concentrations is inactivated in porcine vitreous through autolytic degradation. Autolytic cleavage occurs at a limited number of sites, primarily K156–E157, K166–V167 and R177–V178, which, as predicted, contain a positively-charged arginine or lysine residue at the P1 position. Our data also suggest that autolytic degradation requires at least local or partial unfolding of the protein. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect