Systematic d -Amino Acid Substitutions to Control Peptide and Hydrogel Degradation in Cellular Microenvironments
Year: 2023
Type: article
Abstract: Enzymatically degradable peptides are commonly used as linkers within hydrogels for biological applications; however, controlling the degradation of these engineered peptides with different contexts and cell types can prove challenging. In this work, we systematically examined the substitution of d-amino acids (D-AAs) for different l-amino acids in a peptide sequence commonly utilized in enzymatically degradable hydrogels (VPMS↓MRGG) to create peptide linkers with a range of different degradation times, in solution and in hydrogels, and investigated the cytocompatibility of these materials. We found that increasing the number of D-AA substitutions increased the resistance to enzymatic degradation both for free peptide and peptide-linked hydrogels; yet, this trend also was accompanied by increased cytotoxicity in cell culture. This work demonstrates the utility of D-AA-modified peptide sequences to create tunable biomaterials platforms tempered by considerations of cytotoxicity, where careful selection and optimization of different peptide designs is needed for specific biological applications.
Source: ACS Macro Letters
Institution: University of Delaware
Language: English
Subfield: Molecular Medicine
Domain: Life Sciences
Open Access status: green
Awards: G1177608224, Discovery of Chemical Probes and Therapeutic Leads, Phase II, Unraveling fibrosis with dynamic microenvironments and molecular tools, G4444685404, G5594047776, University of Delaware MRSEC - Center for Hybrid, Active, and Responsive Materials (CHARM), G8414554082, Multiscale considerations for immune engineering at mucosal interfaces
OpenAlex ID: W4376871089