ABSTRACT
Stimuli-responsive hybrid materials that combine the dynamic nature self-assembled organic nanostructures, unique photophysical properties of inorganic materials, and molecular recognition capability of biopolymers can provide sophisticated nanoarchitectures with unprecedented functions. In this report, infrared (IR)-responsive self-assembled peptide-carbon nanotube (CNT) hybrids that enable the spatiotemporal control of bioactive ligand multivalency and subsequent human neural stem cell (hNSC) differentiation are reported. The switching between the ligand presented and hidden states was controlled via IR-induced photothermal heating of CNTs, followed by the shrinkage of the thermoresponsive dendrimers that exhibited lower critical solution temperature (LCST) behavior. The control of the ligand spacing via molecular coassembly and IR-triggered ligand presentation promoted the sequential events of integrin receptor clustering and the differentiation of hNSCs into electrophysiologically functional neurons. Therefore, the combination of our nanohybrid with biomaterial scaffolds may be able to further improve effectiveness, durability, and functionality of the nanohybrid systems for spatiotemporal control of stem cell differentiation. Moreover, these responsive hybrids with remote-controllable functions can be developed as therapeutics for the treatment of neuronal disorders and as materials for the smart control of cell function.
Subject(s)
Nanotubes, Carbon , Biocompatible Materials , Cell Differentiation , Humans , Ligands , Neural Stem Cells , Peptides , Photochemical ProcessesABSTRACT
A new method for the pre-activation cyclization of a long peptide is described. The approach involves the formation of a pre-activated succinimidyl ester species in advance of amidation, which completely eliminates the potentially troublesome amine end-capping side reaction. The cyclization reactions proceed with high efficiency and fast reaction kinetics for the long peptide with 25 residues. The exploration and large-scale preparation of synthetic cyclic peptides should become more accessible and feasible with this approach. This method has a potential to be further applied for the synthesis of much longer and more complex cyclic peptides.
Subject(s)
Amines/chemistry , Peptides, Cyclic/chemistry , Peptides/chemistry , Chemistry Techniques, Analytical , Cyclization , Time FactorsABSTRACT
Macrocycles are interesting molecules because their topological features and constrained properties significantly affect their chemical, physical, biological, and self-assembling properties. In this report, we synthesized unique macrocyclic peptides composed of both an α-helix and a polyproline segment and analyzed their conformational properties. We found that the molecular stiffness of the rod-like polyproline segment and the relative orientation of the two different helical segments strongly affect the efficiency of the macrocyclization reaction. Conformational analyses showed that both the α-helix and the polyproline II helix coexisted within the macrocyclic peptides and that the polyproline segment exerts significant effect on the overall helical stability and conformation of the α-helical segment.
Subject(s)
Peptides , Protein Structure, Secondary , Peptides/chemistryABSTRACT
We present here the development of adaptable hybrid materials in which self-assembling peptides can sense the diameter/curvature of carbon nanotubes and then adjust their overall structures from disordered states to α-helices, and vice versa. The peptides within the hybrid materials show exceptionally high thermal-induced conformational stability and molecular recognition capability for target RNA. This study shows that the context-dependent protein-folding effects can be realized in artificial nanosystems and provides a proof of principle that nanohybrid materials decorated with structured and adjustable peptide units can be fabricated using our strategy, from which smart and responsive organic/inorganic hybrid materials capable of sensing and controlling diverse biological molecular recognition events can be developed.
Subject(s)
Nanotechnology/methods , Peptides/chemistry , Protein Structure, Secondary , Adsorption , Amino Acid Sequence , Colloids/chemistry , Microscopy, Electron, Transmission , Models, Molecular , Molecular Sequence Data , Nanoparticles/chemistry , Nanotubes, Carbon/chemistry , Protein Folding , RNA/chemistry , Temperature , rev Gene Products, Human Immunodeficiency Virus/chemistryABSTRACT
A novel strategy to stabilize the α-helical secondary structures of peptides upon binding to gold nanoparticles is described. Using a model protein-protein interaction system, we showed that AuNPs decorated with stabilized p53 α-helix peptides can mediate specific molecular recognition with their target protein.
Subject(s)
Gold/chemistry , Metal Nanoparticles/chemistry , Peptides/chemistry , Circular Dichroism , Peptides/metabolism , Protein Structure, Secondary , Surface Properties , Tumor Suppressor Protein p53/chemistryABSTRACT
Here we ask the fundamental questions about the effect of peptide topology on self-assembly. The study revealed that the self-assembling behaviors of cyclic and linear peptides are significantly different in several respects, in addition to sharing several similarities. Their clear differences included the morphological dissimilarities of the self-assembled nanostructures and their thermal stability. The similarities include their analogous critical aggregation concentration values and cytotoxicity profiles, which are in fact closely related. We believe that understanding topology-dependent self-assembly behavior of peptides is important for developing tailor-made self-assembled peptide nanostructures.
