(326g) Designing Heterochiral Coiled Coils for Enhanced Binding and Enzymatic Stability in Biomaterials
AIChE Annual Meeting
2022
2022 Annual Meeting
Materials Engineering and Sciences Division
Biomimetic Materials I
Tuesday, November 15, 2022 - 2:36pm to 2:54pm
Coiled coils are common α-helical structural motifs found in proteins. These supramolecular and dynamic coiled coil complexes that play a role in protein folding are now prominent features of dynamic biomaterials, drug delivery, and patterning platforms. However, since natural l-peptides suffer from rapid enzymatic degradation, in vivo applications may be limited. We hypothesized that forming coiled coils from heterochiral d- and l-peptides, as opposed to homochiral complexes formed of only naturally occurring l-peptides, will enhance the enzymatic stability of coiled coil complexes and make available a larger range of binding strengths between coiled coil peptides. However, we found that simply switching the stereochemistry of previously reported glutamic acid/lysine (E/K)-rich coils with a heptad repeating structure to heterochiral rather than homochiral disrupts coiled coil formation. Based on previous reports indicating that coiled coils with a hendecad repeat structure can form heterochiral complexes, we designed (E/K)-rich coiled coils with a hendecad repeat structure. We demonstrated that our designed hendecad coiled coils form complexes by isothermal titration calorimetry (ITC). In comparison to homochiral complexes formed by these hendecad coiled coils, we found that the heterochiral peptides formed complexes with 2.5 times greater heats by ITC, supporting our hypothesis that heterochiral complexes increase the available range of binding strengths. In addition to ITC results for the binding characteristics of these peptides, we will also discuss the enzymatic stability of these complexes. We are encouraged by these results that indicate we can engineer patterning and biomaterials platforms capable of operating in enzyme-laden biological environments.