Peptide-Modified Surfaces for Binding Carbamylated Proteins from Plasma.

Area of Science:

• Biomaterials Science
• Protein Chemistry
• Nephrology

Background:

• Carbamylation of blood proteins is a detrimental post-translational modification associated with kidney dysfunction and poor patient outcomes in hemodialysis.
• Identifying effective methods for removing carbamylated proteins is crucial for improving patient health during dialysis.

Purpose of the Study:

• To design and evaluate a novel peptide-functionalized surface for the selective adsorption of carbamylated plasma proteins, specifically carbamylated albumin (cHSA) and carbamylated fibrinogen (cFgn).
• To compare the efficacy of different peptide functionalizations (NH-cH2p1 vs. CO-cH2p1) and assess surface performance in diluted plasma.

Main Methods:

• Preparation of poly(hydroxyethyl methacrylate) (p(HEMA)) surfaces using surface-initiated atom transfer radical polymerization (SI-ATRP).
• Functionalization of p(HEMA) surfaces with a specific peptide (cH2p1) to create selective binding sites.
• Evaluation of protein adsorption selectivity for carbamylated versus native proteins (cHSA, cFgn) and assessment of platelet compatibility.

Main Results:

• The cH2p1-functionalized surfaces demonstrated selective binding of carbamylated albumin (cHSA) and carbamylated fibrinogen (cFgn) over their native counterparts.
• The NH-cH2p1 functionalization exhibited superior selectivity compared to CO-cH2p1.
• High adsorption capacity for carbamylated proteins was maintained in diluted plasma, with minimal adsorption of native fibrinogen.
• The NH-cH2p1 surface showed low platelet adhesion and activation, indicating good hemocompatibility.

Conclusions:

• Peptide-functionalized p(HEMA) surfaces, particularly with NH-cH2p1, are effective for the selective removal of carbamylated plasma proteins.
• This approach holds potential for developing improved hemodialysis strategies by targeting harmful protein modifications.
• The designed surface exhibits favorable hemocompatibility, crucial for biomedical applications.