Supramolecular Nanostructures with Tunable Donor Loading for Controlled H₂S Release

Abstract

Hydrogen sulfide (H 2 S), an endogenously generated and regulated signaling gas, plays a vital role in a variety of (patho)physiological processes. In the past few years, different kinds of H 2 S-releasing compounds (often referred to as H 2 S donors) have been developed for H 2 S delivery, but it is still challenging to make H 2 S donors with tunable payloads in a simple and efficient manner. Herein, a series of peptide-H 2 S donor conjugates (PHDCs) with tunable donor loadings are designed for controlled H 2 S release. The PHDCs self-assemble into nanoribbons with different geometries in aqueous solution. Upon the addition of cysteine, these nanostructures release H 2 S, delivering their payload into H9C2 cells, as visualized using an H 2 S-selective fluorescent probe. Beyond imaging, in vitro studies show that the ability of PHDCs to mitigate doxorubicin-induced cardiotoxicity in H9C2 cardiomyocytes depends on their nanostructures and H 2 S release profiles. This strategy may enable the development of sophisticated H 2 S-releasing biomaterials for drug delivery and regenerative medicine.

A combined experimental and computational approach reveals how aromatic peptide amphiphiles self-assemble to form ion-conducting nanohelices

“…This is consistent with previous CAC measurements on similar APAs. 18,29,39,40 CD spectroscopy revealed that the secondary structures of these peptide nanoassemblies were similar, and both displayed strong signals in the peptide region (190-240 nm) and in the SATO characteristic absorption region (300-360 nm), consistent with SATO absorptions in the corresponding UV−vis spectra (Fig. S6).…”

Crescent-Shaped Supramolecular Tetrapeptide Nanostructures

“…To make the PHDCs, we prepared a peptide of the structure AdK S K S EE (Ad = adamantyl group, K S = lysine residue functionalized with an H 2 S-releasing S -aroylthiooxime (SATO) group, E = glutamic acid residue; Figure A). We originally developed the SATO group because of its ability to generate H 2 S in response to thiols, but we found that its inclusion in peptides generates a variety of self-assembled morphologies; for example, PHDCs containing two K S and two E residues form persistent nanohelices or nanoribbons of various sizes depending on the specific sequence. − Here, we included for the first time the bulky Ad group with the idea that it would provide additional hydrophobic interactions beyond those of the SATO groups, while also contributing steric hindrance during the self-assembly process. Detailed synthetic procedures and characterization can be found in the Supporting Information (Figures S1 and S2).…”

“…Among the classes of synthetic small molecules capable of self-assembly into nanostructures, peptides are perhaps the most widely studied because of their biodegradability, high degree of tunability, and capacity for several types of noncovalent interactions. ,,− Beyond this, they can be quickly synthesized and purified with direct sequence control. Our group is interested in the aqueous self-assembly of short peptides and peptide derivatives into unusual nanostructures and their applications in biology and other areas. − Here, we report on our recent discovery of an aromatic peptide amphiphile that self-assembles into crescent-shaped nanostructures. Crescent-shaped inorganic nanostructures have been prepared through various means, and their crescent shape affords unique properties. − In contrast, it remains a great challenge to produce crescent nanostructures from peptides, or any small organic molecule, through a direct self-assembly approach.…”

“…H 2 S was long thought to be only a poisonous gas, but its biological signaling roles were discovered in 1996 . Since then, a wide variety of studies have shown that H 2 S mediates numerous (patho)­physiological processes, including vasorelaxation, oxidative stress reduction, and inflammation. − However, these results were mainly acquired by using inorganic sulfide salts such as sodium sulfide (Na 2 S) or sodium hydrosulfide (NaSH) as H 2 S sources. , Recognizing that these sulfide salts were not ideal compounds for studying H 2 S biology, researchers have developed several classes of stimuli-responsive, H 2 S-releasing compounds (termed H 2 S donors) over the past several years. − H 2 S donors with targeting capabilities and varying release rates have shown that the method of delivery can greatly influence the bioactivity of this gas. , However, despite this progress, most H 2 S donors lack good water solubility and have limited means for cell internalization, hindering H 2 S-based treatments because of the reactive and transient nature of this signaling molecule. On the basis of our discovery of a short peptide capable of releasing H 2 S that self-assembles into crescent nanostructures (Figure A,B), we asked how the crescent shape would influence the bioactivity of this uniquely shaped H 2 S donor.…”

Chiral Orchestration: A Tool for Fishing Out Tripeptide-Based Mechanoresponsive Supergelators Possessing Anti-Inflammatory and Antimicrobial Properties

“…Smart and selective therapeutic approaches derived from stimuli-responsive peptide-based hydrogels invite immense interest from diverse segments of science. − Cost-effectiveness, biocompatibility, control over structural diversity, and involvement of noncovalent interactions have propelled the idea of harnessing the process of self-assembly of peptides for tackling various aspects related to biomedical applications. − Commonly, the stimuli that nucleate the self-assembly phenomena are heat, light, pH, ionic strength, ultrasound, enzymes, and others. − However, these stimuli often take the back seat as they hamper the inherent properties of the molecules due to the utilization of high energy or foreign chemicals. However, exploration of mechanoresponsive hydrogels still remains in its infancy. − In particular, mechanoresponsive (thixotropic) hydrogels are advantageous over others owing to the ease of sol–gel transition commenced simply through mechanical force initiation .…”