Morphology Transformation via pH-Triggered Self-Assembly of Peptides

Three flexible peptides (P1: (C₁₇H₃₅CO-NH-GRGDG)₂KG; P2: (Fmoc-GRGDG)₂KG; P3: (CH₃CO-NH-GRGDG)₂KG) self-assembled to form a variety of morphologically distinct assemblies at different pHs. P1 formed nanofibers at pH 3, then self-assembled into nanospheres with pH up to 6 and further changed to lamellar structures when the pH value was further increased to 10. P2 aggregated into an entwined network structure at pH 3, and then self-assembled into well-defined nanospheres, lamellar structures, and vesicles via adjusting the pH value. However, P3 did not self-assemble into well-ordered nanostructures, presumably due to the absence of a large hydrophobic group. The varying self-assembly behaviors of the peptides at different pHs are attributed to molecular conformational changes. These self-assembled supramolecular materials might contribute to the development of new peptide-based biomaterials

Weak Alignment Liquid Crystal Media from Colloidal Dispersion and Self-assembled Oligopeptide for Anisotropic NMR

ConspectusAcquiring anisotropic NMR parameters such as residual dipolar couplings (RDCs) and residual chemical shift anisotropies (RCSAs) has been demonstrated as a powerful route to elucidate the three-dimensional structure of organic molecules in organic and medicinal chemistry. However, this methodology is somewhat compromised by the limited availability of alignment media, which are indispensable to induce the partial orientation of analytes for anisotropic data acquisition. Given the feature of inherent anisotropy, lyotropic liquid crystals (LLCs) have been documented as excellent candidates to act as alignment media. This Account aims to review the research progress of developing LLCs to obtain anisotropic NMR data. We mainly focus on two complementary LC media, i.e., two-dimensional (2D) colloidal dispersions and self-assembled peptides, that are generated by a “top-down” approach and “bottom-up” approach, respectively.Our laboratory has been at the forefront of developing 2D colloidal dispersions as alignment media. We first demonstrated the applicability of graphene oxide (GO) LLCs in the RDC-based structural elucidation of small molecules. When used as alignment media, GO LLCs showed a striking feature of no background signals. Clean NMR spectra enable accurate data assignment without disturbances and even effective RDC measurements of rare natural products. To circumvent the limitation that preparing GO LLC media needs tedious solvent exchange to remove nondeuterated solvents for NMR experiments, we subsequently developed MXene LLCs. Different from GO media whose anisotropy would be destroyed after direct freeze-drying, MXene can self-align in the redispersed solution to recover LC behavior. This feature provides great convenience for sample preservation and rapid medium preparation. Another advantage of MXene LLCs over GO media is the applicability to directly measure RDCs of aromatic solutes with no need for chemical modification on MXenes.To complement the 2D colloidal media that are only compatible with strong polar solvents, we further develop supramolecular LLCs. Oligopeptides, due to their mature synthesis strategy, structural designability, and robust self-assembly ability, have been exploited to create supramolecular alignment media in different solvents. We first reported CH3OH-, DMSO-, and multiple solvent-compatible peptide media, which show the broad applicability of their corresponding analytes. Meanwhile, the chiral amino acids confer oligopeptide LLCs with potential chirality, and we have demonstrated their relative application of enantiodiscrimination. Arising from the structural diversity of oligopeptides, several distinct LLC media are constructed and applied to measure independent sets of RDCs. This offers an opportunity for de novo structural determination of organic molecules.In light of the good fluidity of these media, analytes can rapidly penetrate the LLC phases for self-alignment, facilitating simple and fast NMR experiments. Moreover, the alignment degree can be easily scaled through varying LC concentrations. This enables precise and accurate data acquisition at an optimal alignment strength. In addition to describing the design and LC preparation, we show the applicability of these weak alignment media for acquiring anisotropic NMR parameters. We hope it can serve as an inspiration source for the exploration of new alignment media, NMR methodology, and related material science

An H₂S‑Regulated Artificial Nanochannel Fabricated by a Supramolecular Coordination Strategy

Hydrogen sulfide (H2S), as the third gasotransmitter, has an important impact on physiological and pathological activities. Herein, we fabricated an artificial nanochannel with a conductance value of 2.01 nS via a supramolecular coordination strategy. Benefiting from the unique H2S-mediated covalent reaction, the nanochannel biosensor could change from ON to OFF states with the addition of H2S. Furthermore, this nanochannel directed the ion transport, showing a high rectification ratio as well as gating ratio. Subsequently, theoretical simulations were conducted to help to reveal the possible mechanism of the functionalized nanochannel. This study can provide insights for better understanding the process of H2S-regulated biological channels and fabricating gas gated nanofluids

An H₂S‑Regulated Artificial Nanochannel Fabricated by a Supramolecular Coordination Strategy

Hydrogen sulfide (H2S), as the third gasotransmitter, has an important impact on physiological and pathological activities. Herein, we fabricated an artificial nanochannel with a conductance value of 2.01 nS via a supramolecular coordination strategy. Benefiting from the unique H2S-mediated covalent reaction, the nanochannel biosensor could change from ON to OFF states with the addition of H2S. Furthermore, this nanochannel directed the ion transport, showing a high rectification ratio as well as gating ratio. Subsequently, theoretical simulations were conducted to help to reveal the possible mechanism of the functionalized nanochannel. This study can provide insights for better understanding the process of H2S-regulated biological channels and fabricating gas gated nanofluids

Peptide-Based Vector of VEGF Plasmid for Efficient Gene Delivery <i>in Vitro</i> and Vessel Formation <i>in Vivo</i>

Critical limb ischemia is regarded as a potentially lethal disease, and the treatment effects of existing therapies are limited. Here, in order to develop a potential approach to improve the therapy effects, we designed a peptide of TAT-PKKKRKV as the vector for VEGF₁₆₅ plasmid to facilitate <i>in vivo</i> angiogenesis. In <i>in vitro</i> studies, TAT-PKKKRKV with low cytotoxicity exhibited efficient transfection ability either with or without serum. Additionally, application of TAT-PKKKRKV/VEGF₁₆₅ complexes in hindlimb ischemia rats obviously promoted the expression of VEGF protein, which further enhanced effective angiogenesis. The results indicated that TAT-PKKKRKV is an efficient gene vector with low toxicity both <i>in vitro</i> and <i>in vivo</i>, which has great potential for clinical gene therapy

Self-Assembly of Hybridized Peptide Nucleic Acid Amphiphiles

In this report, a series of peptide nucleic acid amphiphiles (PNAAs) with hybridization properties were designed and synthesized. Driven by hydrophobic interaction, the hybridized PNAAs can form uniform micelles, the base stacking interaction from PNA segments further stabilized the micelles. The effects of hydrophobic alkyl chain length, structure of hydrophilic peptides, concentration, and pH on the self-assembly behavior of partly complementing PNAA duplexes were explored

Evaluating the Effects of Charged Oligopeptide Motifs Coupled with RGD on Osteogenic Differentiation of Mesenchymal Stem Cells

Mesenchymal stem cells, due to their multilineage differentiation potential, have emerged as a promising cell candidate for cell-based therapy. In recent years, biomaterials were artificially synthesized to control the differentiation of mesenchymal stem cells. In this study, a series of charged or neutral oligopeptide motifs coupled with RGD were synthesized and used for surface modification using quartz substrates as model. Cell behaviors on the modified surfaces with different charged oligopeptide motifs were studied. It was found that these different charged oligopeptide motifs coupled with RGD were biocompatible for cell proliferation and adhesion. Moreover, it was demonstrated that the positively charged oligopeptide motif could inhibit osteogenic differentiation, while the negatively charged and neutral oligopeptide motifs could enhance osteogenic differentiation in the presence of RGD. This work may bring us enlightenment that different charged oligopeptide motifs coupled with RGD may be used for biomaterial surface modification for different stem cell-based therapies