Abstract
Synthetic assembly within living cells represents an innovative way to explore purely chemical tools that can direct and control cellular behavior. We use a simple and modular platform that is broadly accessible and yet incorporates highly intricate molecular recognition, immolative, and rearrangement chemistry. Short bimodular peptide sequences undergo a programmed sequence of events that can be tailored within the living intracellular environment. Each sequential stage of the pathways beginning with the cellular uptake, intracellular transport, and localization imposes distinct structural changes that result in the assembly of fibrillar architectures inside cells. The observation of apoptosis, which is characterized by the binding of Annexin V, demonstrates that programmed cell death can be promoted by the peptide assembly. Higher complexity of the assemblies was also achieved by coassembly of two different sequences, resulting in intrinsically fluorescent architectures. As such, we demonstrate that the in situ construction of architectures within cells will broaden the community’s perspective toward how structure formation can impact a living system.
Highlights
Supramolecular interactions govern core aspects of cellular life where they are omnipresent in every biological pathway
Solid-phase peptide synthesis using fluorenylmethoxycarbonyl (Fmoc) chemistry was conducted with alanine-preloaded Wang resin (Scheme 1)
Fmoc-serine was added as the second amino acid usingtripyrrolidinophosphonium hexafluorophosphate (PyBOP) and N,N-diisopropylethylamine (DIPEA).[24]
Summary
Supramolecular interactions govern core aspects of cellular life where they are omnipresent in every biological pathway. O,N-acyl rearrangement to generate the self-assembling peptide sequence In this way, intracellular transport, release, and supramolecular assembly into peptide fibrils is individually and sequentially programmed inside different cellular compartments by consecutive chemical reactions (Figure 1). We demonstrate coassembly as a strategy to increase the level of functionality by imparting fluorescence into the fibrillar structures to allow imaging.[19,20] Coassembly, i.e., assembly of more than a single component, is prevalent in Nature, and important examples include the assembly of α-/βtubulin in microtubules,[21] cholesterol/phospholipids in membranes,[22] or the Arp2/3 complex in actins.[23] While Nature uses highly specific proteins to transport and program these assemblies, synthetic methods are advantageous as they can be bioorthogonal and be tailored. By incorporating sophisticated chemical designs into a simple bimodular peptide sequence, we demonstrate that synthetic architectures can be formed directly within living systems using natural triggers
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
