Nature's Design Principles Research Articles

Facile synthetic method for peptoids bearing multiple azoles on side chains

AbstractNatural metalloenzymes stabilize metal centers by utilizing multiple imidazole moieties. Inspired by nature's design principles, the introduction of multiple azoles into ligands has been an effective method for constructing transition metal complexes. Herein, we describe a post‐synthetic modification of peptoids to incorporate multiple azoles on side chains. A simple substitution reaction between an azole (imidazole, pyrazole, 1,2,3‐triazole, and tetrazole) and a chloroalkyl‐containing peptoid provided access to a variety of azole‐containing peptoids. Ten azole‐containing peptoids were synthesized from a single chloroalkyl‐containing peptoid, and the efficiency of each azole for the substitution reaction was evaluated. We have identified that several of the azole‐containing peptoids are capable of binding with Cu(II) and Fe(III). Our synthetic approach can contribute to the expansion of peptoids' chemical diversity and the development of novel peptoids for metal recognition and catalysis.

Frenkel excitons in heat-stressed supramolecular nanocomposites enabled by tunable cage-like scaffolding.

Delocalized Frenkel excitons-coherently shared excitations among chromophores-are responsible for the remarkable efficiency of supramolecular light-harvesting assemblies within photosynthetic organisms. The translation of nature's design principles to applications in optoelectronic devices has been limited by the fragility of the supramolecular structures used and the delicate nature of Frenkel excitons, particularly under mildly changing solvent conditions and elevated temperatures and upon deposition onto solid substrates. Here, we overcome those functionalization barriers through composition of stable supramolecular light-harvesting nanotubes enabled by tunable (~4.3-4.9 nm), uniform (±0.3 nm) cage-like scaffolds. High-resolution cryogenic electron microscopy, combined with scanning electron microscopy, broadband femtosecond transient absorption spectroscopy and near-field scanning optical microscopy revealed that excitons within the cage-like scaffolds are robust, even under extreme heat stress, and control over nanocomposite dimensions is maintained on solid substrates. Our bio-inspired nanocomposites provide a general framework for the development of next-generation organic devices made from stable supramolecular materials.

Engineering an Anti-Arrhythmic Calmodulin

The cardiac ryanodine receptor (RYR2) is a critical Ca²+ handling protein. Several post-translational modifications, mutations, and altered interactions between RYR2 and its regulatory proteins can all increase the RYR2 open probability (P0), disrupting normal Ca²+ handling, leading to arrhythmia. There is a great need for therapeutic strategies that decrease RYR2 P0. Normally, calmodulin (CaM) decreases RYR2 P0, decreasing Ca²+ sparks and waves. Naturally occurring mutations in CaM have recently been identified that instead increase RYR2 P0 and cause arrhythmia. Using these CaM mutations as tools, we have discovered that the N-terminal rate of Ca²+ dissociation from the CaM-RYR2 complex is an important factor that modulates RYR2 inhibition by CaM. That is, the longer Ca²+ remains bound to the CaM-RYR2 complex the longer RYR2 remains refractory, ultimately influencing the frequency of cardiac myocyte sparks and waves. We hypothesize that slowing the N-terminal Ca²+ dissociation rate from CaM bound to RYR2 will decrease RYR2 P0 and prevent arrhythmias. Using both rational engineering (GSH M37Q CaM) and nature's design principles (soybean CaM4) to sensitize CaM to Ca²+, we are attempting to create therapeutic CaMs against defective RYR2 regulation. Excitingly, our therapeutic GSH M37Q CaM decreases the arrhythmogenic potential of myocytes isolated from the pro-arrhythmic calsequestrin knockout mouse. Thus, tuning CaM's regulation of RYR2 through Ca²+ dissociation is a viable therapeutic strategy to prevent arrhythmia.

Ruled surface underlying KcsA potassium channels

Recent experiments have revealed that the opening and closing of the channel is controlled by concertedly rotating and tilting the ends of the alpha-helices in the KcsA ion channels. We recognize these transmembrane alpha-helices as the generating lines of the ruled surface: the hyperboloid of one sheet. The twist-to-shrink feature of the hyperboloid is adopted by KcsA channels in gating the pore as observed in experiments. Our model may shed light on understanding nature's design principles of ion channels. And the conclusions drawn from this study have implications for the design of artificial channels.

Materials Taking a Lesson from Nature

Structural biomaterials with their often extraordinary properties and versatile functions are typically constructed from very limited sets of building blocks and types of supramolecular interactions. In this review we discuss how, inspired by nature's design principles for protein-based materials, oligopeptide-modified polymers can be used as a versatile toolbox to program nanostructure and hierarchical structure formation in synthetic materials.