Chondroitin sulfate-binding peptides

Chondroitin sulfate (CS) is the predominant glycosaminoglycan (GAG) found in the body and plays an important role in the central nervous system (CNS). Recent studies have shown that the pattern of sulfation groups on the GAG chain affects cell behavior. Specifically, there is an increase in chondroitin 6-sulfate (C6S) expression following spinal cord injury (SCI) that contributes to the inhibitory environment preventing axonal regeneration. However, in vitro studies of the effects of different types of CS on neuron behavior yield conflicting results. A major obstacle in understanding the role of CS in the CNS is the lack of known CS-binding peptide sequences. Therefore, the goal of this study is to understand the role of CS in the CNS through the development of CS-binding peptides for the treatment of SCI.;CS-binding peptides were identified through peptide array screening and characterized for sequence composition. Compositional characterization of the CS-binding peptides showed which amino acids were important for CS-binding affinity leading to the development of CS-binding peptides with higher CS-binding affinity. An in vitro model of SCI was developed with neurons cultured on C6S coated slides which inhibited neurite outgrowth. CS-binding peptides were added to C6S inhibited neurons and increased neurite outgrowth to effectively block C6S inhibition. This result showed that CS-binding peptides are a potential treatment for nerve regeneration following SCI. The CS-binding peptides were also used to incorporate C6S and NGF in gels for an affinity-based neural tissue engineering model. The results from this study showed that CS-binding peptides and C6S are both important for slow NGF release from PEG gels to increase neurite outgrowth to overcome the inhibitory effects of C6S. In this study, CS-binding peptides were developed to better understand the role of CS in the CNS for the treatment of SCI.