Exponential Activation of Carbonic Anhydrase by Encapsulation in Dynameric Host Matrices with Chiral Discrimination

Abstract

Herein an unexpected exponential activation of bovine carbonic anhydrase (bCA) in aqueous solutions in the presence of dynameric host matrices is reported. Successive experiments confirmed the important role of dynamic imine exchange within the dynameric host structures for direct enzyme activation. This allows for optimal encapsulation of the guest enzyme, whereas the presence of external proton-sponge amino groups is less important. Non-exchanging polymeric sec-amine congeners formed from imine reduction of dynameric structures show no obvious activation on bCA. Although the dynamers synthesized from diamino chiral-pair precursors displayed similar activation constants toward bCA, different activation delay times were observed from these two dynamers of opposite optical activity. The circular dichroism (CD) spectra demonstrate selective structural changes in the secondary structure of bCA upon dynameric encapsulation in aqueous solution. The different interaction molds observed in CD spectra for the dynamers with opposite chirality explain the longer activation time required for one of the dynamers.

Dynamic covalent polymers for biomedical applications

“…Other amines, including the linear 1,3-diaminopropane (5), the branched tris(2-aminoethyl)amine (7), and the chiral 1,2diamino cyclohexane (9-10), have also been used to synthesize dynamic covalent polymers (Figure 11), and tested for their influences on the activity of carbonic anhydrase. 139 All these amines also resulted in decent activation effects, but generally with lower activation constants than amines 3-4, demonstrating the importance of amide-induced H-bonding effects. Unexpectedly, an exponential increase in the enzyme-catalyzed product formation was observed for the polymeric structures with optical activity, such as dynamers based on amines 9-10, indicating the requirement for a pre-organization period that enable the adaptive encapsulation of the enzyme by the dynameric matrices.…”

“…The polymers form an adaptable matrix around the enzyme molecules, thereby leading to a significantly increased enzyme activity (Figure 10). [137][138][139] Figure 10. Concept of enzyme activation by direct addition of dynamers.…”

Dynamic Hydrogels Based on Double Imine Connections and Application for Delivery of Fluorouracil

“…The reversibly covalent bonds, such as imine, hydrazine, and disulfide, etc. have provided dynamic features to the polymers, leading to responsivity to different stimuli, including pH (Charbonneau et al, 2011 ), light (Fuhrmann et al, 2016 ), and biological targets, for example, enzymes (Zhang et al, 2016a , b , 2018b ) and DNA (Catana et al, 2015 ; Clima et al, 2015 ; Zhang et al, 2018a ).…”

Molecular Networks in Dynamic Multilevel Systems

“…The use of dynamic covalent chemistry has led to the preparation of responsive polymer materials with avariety of properties. [36][37][38][39][40] Althoughs ome polymers based on two orthogonal reversible reactions have been reported, [41][42][43] multi-responsive systemsb ased on the combination of several reversible reactions have not been investigated.…”