Design and synthesis of a nucleobase functionalized peptide hydrogel: in vitro assessment of anti-inflammatory and wound healing effects.

Over the past several years, a significant increase in the expanding field of biomaterial sciences has been observed due to the development of biocompatible materials based on peptide derivatives that have intrinsic therapeutic potential. In this report, we synthesized nucleobase functionalized peptide derivatives (NPs). Hydrogelation in the synthesized NPs was induced by increasing their hydrophobicity with an aromatic moiety. The aggregation behavior of the NPs was analyzed by performing molecular dynamics simulations and DOSY NMR experiments. We performed circular dichroism (CD), thioflavin-T binding and PXRD to characterize the supramolecular aggregation in the NP1 hydrogel. The mechanical strength of the NP1 hydrogel was tested by performing rheological experiments. TEM and SEM experiments were performed to investigate the morphology of the NP1 hydrogel. The biocompatibility of the newly synthesized NP1 hydrogel was investigated using McCoy and A549 cell lines. The hemolytic activity of the NP1 hydrogel was examined in human blood cells. The stability of the newly formed NP1 hydrogel was examined using proteinase K and α-chymotrypsin. The NP1 hydrogel was used for in vitro wound healing. Western blotting, qRT-PCR and DCFDA assay were performed to determine the anti-inflammatory activity of the NP1 hydrogel. The synthesized NP1 hydrogel also exhibits antibacterial efficacy.

Sonication-Induced Boladipeptide-Based Metallogel as an Efficient Electrocatalyst for the Oxygen Evolution Reaction.

Bioinspired, self-assembled hybrid materials show great potential in the field of energy conversion. Here, we have prepared a sonication-induced boladipeptide (HO-YF-AA-FY-OH (PBFY); AA = Adipic acid, F = l-phenylalanine, and Y = l-tyrosine) and an anchored, self-assembled nickel-based coordinated polymeric nanohybrid hydrogel (Ni-PBFY). The morphological studies of hydrogels PBFY and Ni-PBFY exhibit nanofibrillar network structures. XPS analysis has been used to study the self-assembled coordinated polymeric hydrogel Ni-PBFY-3, with the aim of identifying its chemical makeup and electronic state. XANES and EXAFS analyses have been used to examine the local electronic structure and coordination environment of Ni-PBFY-3. The xerogel of Ni-PBFY was used to fabricate the electrodes and is utilized in the OER (oxygen evolution reaction). The native hydrogel (PBFY) contains a gelator boladipeptide of 15.33 mg (20 mmol L-1) in a final volume of 1 mL. The metallo-hydrogel (Ni-PBFY-3) is prepared by combining 15.33 mg (20 mmol L-1) of boladipeptide (PBFY) with 3 mg (13 mmol L-1) of NiCl2·6H2O metal in a final volume of 1 mL. It displays an ultralow Tafel slope of 74 mV dec-1 and a lower overpotential of 164 mV at a 10 mA cm-2 current density in a 1 M KOH electrolyte, compared to other electrocatalysts under the same experimental conditions. Furthermore, the Ni-PBFY-3 electrocatalyst has been witnessed to be highly stable during 100 h of chronopotentiometry performance. To explore the OER mechanism in an alkaline medium, a theoretical calculation was carried out by employing the first-principles-based density functional theory (DFT) method. The computed results obtained by the DFT method further confirm that the Ni-PBFY-3 electrocatalyst has a high intrinsic activity toward the OER, and the value of overpotential obtained from the present experiment agrees well with the computed value of the overpotential. The biomolecule-assisted electrocatalytic results provide a new approach for designing efficient electrocatalysts, which could have significant implications in the field of green energy conversion.

Design and Development of Sustainable Cu2 (II)- and Mn2 (III)-Embedded Bifunctional Electrocatalysts: Enhanced Hydrogen and Oxygen Generation.

Nowadays, environmentally friendly, low-cost-effective, and sustainable electrocatalysts used widely for hydrogen and oxygen evolution reactions have come into the limelight as a new research topic for scientists. This study highlights the preparation of two unique and symmetrical dinuclear Cu (II) and Mn (III) bifunctional catalysts by a facile simple slow evaporation and diffusion route. [C32H24Cu2F4N4O4] (1) and [C32H24Mn2F4N4O4] (2) both have monoclinic (C2/c (15)) crystal systems, with oxidation states +2 and +3, respectively. Prominent SPR peaks at 372 and 412 nm indicate an M-L charge transfer transition in both complexes. The synthesized electrocatalysts display exceptional catalytic activity for the hydrogen evolution reaction (HER) and oxygen evolution reaction (OER). Complex 1 exhibits enhanced hydrogen generation in 0.5 M H2SO4 with a small overpotential of 216 mV at -10 mA cm-2 along with a significantly lower Tafel value of 97 mV/dec compared to Complex 2. Moreover, Complex 1 is highly active for the OER in 1 M KOH with a small Tafel slope of 103 mV/dec and a low overpotential of 340 mV to acquire 10 mA cm-2 current density, compared to Complex 2. Complex 1 and Complex 2 remain stable up to 20 h in acidic electrolyte and up to 36 h and 20 h in the basic electrolyte, respectively.

Synthesis and Structural Studies of Nucleobase Functionalized Hydrogels for Controlled Release of Vitamins.

The development of biomolecule-derived biocompatible scaffolds for drug delivery applications is an emerging research area. Herein, we have synthesized a series of nucleobase guanine (G) functionalized amino acid conjugates having different chain lengths to study their molecular self-assembly in the hydrogel state. The gelation properties have been induced by the correct choice of chain lengths of fatty acids present in nucleobase functionalized molecules. The effect of alkali metal cations, pH, and the concentration of nucleobase functionalized amino acid conjugates in the molecular self-assembly process has been explored. The presence of Hoogsteen hydrogen bonding interaction drives the formation of a G-quadruplex functionalized hydrogel. The DOSY nuclear magnetic resonance is also performed to evaluate the self-assembling behavior of the newly formed nucleobase functionalized hydrogel. The nanofibrillar morphology is responsible for the formation of a hydrogel, which has been confirmed by various microscopic experiments. The mechanical behaviors of the hydrogel were evaluated by rheological experiments. The in vitro biostability of the synthesized nucleobase amino acid conjugate is also investigated in the presence of hydrolytic enzymes proteinase K and chymotrypsin. Finally, the nucleobase functionalized hydrogel has been used as a drug delivery platform for the control and sustained pH-responsive release of vitamins B2 and B12. This synthesized nucleobase functionalized hydrogel also exhibits noncytotoxic behavior, which has been evaluated by their in vitro cell viability experiment using HEK 293 and MCF-7 cell lines.

Sodium Alginate-CuS Nanostructures Synthesized at the Gel-Liquid Interface: An Efficient Photocatalyst for Redox Reaction and Water Remediation.

The use of visible light to propel chemical reactions is an exciting area of study that is crucial in the current socioeconomic environment. However, various photocatalysts have been developed to harness visible light, which consume high energy during synthesis. Thus, synthesizing photocatalysts at gel-liquid interfaces in ambient conditions is of scientific importance. Herein, we report an environmentally benign sodium alginate gel being used as a biopolymer template to synthesize copper sulfide (CuS) nanostructures at the gel-liquid interface. The driving force for the synthesis of CuS nanostructures is varied by changing the pH of the reaction medium (i.e., pH 7.4, 10, and 13) to tailor the morphology of CuS nanostructures. The CuS nanoflakes obtained at pH 7.4 transform into nanocubes when the pH is raised to 10, and the nanostructures deform at the pH of 13. Fourier transform infrared spectroscopy (FTIR) confirms all the characteristic stretching of sodium alginate, whereas the CuS nanostructures are crystallized in a hexagonal crystal system, as revealed by the powder X-ray diffraction analysis. The high-resolution X-ray photoelectron spectroscopy (XPS) spectra show the +2 and -2 oxidation states of copper (Cu) and sulfur (S) ions, respectively. The CuS nanoflakes physisorbed a higher concentration of greenhouse CO2 gas. Owing to a lower band gap of CuS nanoflakes synthesized at a pH of 7.4, compared to other CuS nanostructures prepared at pH 10 and 13, CuS photocatalytically degrades 95% of crystal violet and 98% of methylene blue aqueous dye solutions in 60 and 90 min, respectively, under blue light illumination. Additionally, sodium alginate-copper sulfide (SA-CuS) nanostructures synthesized at a pH of 7.4 demonstrate excellent performance in photoredox reactions to convert ferricyanide to ferrocyanide. The current research opens the door to developing new photocatalytic pathways for a wide range of photochemical reactions involving nanoparticle-impregnated alginate composites prepared on gel interfaces.

Dynamic Multicomponent Reactions-Directed Self-Assembled G-quadruplex Inherent Antibacterial Hydrogel.

Nowadays, inherent antibacterial hydrogels have gained significant attention due to their utilization against infectious bacteria. Herein, we focus on the development of an injectable, self-healable, dynamic, and G-quadruplex hydrogel with inherent antibacterial activity. The dynamic self-assembled hydrogel is constructed upon multicomponent reactions (MCR) among guanosine, 2-formylphenylboronic acid, and amino acid/peptides in the presence of potassium ions. The role of amino acid/peptides in the formation of the G-quadruplex hydrogel is studied in detail. The G-quadruplex structure is formed via the π-π stacking of G-quartets. The formation of G-quadruplex is investigated by thioflavin T binding assay, CD spectroscopy, and PXRD. The formation of the dynamic imino-boronate bond in the hydrogels is well characterized by temperature-dependent 11B NMR (VT-NMR) and FT-IR spectroscopy. Furthermore, HR-TEM images and rheological experiments reveal the fibrillar networks and viscoelastic property of the hydrogels. The presence of the dynamic imino-boronate ester bonds makes the hydrogel injectable and self-healable in nature. These dynamic G-quadruplex hydrogels show potential antibacterial activity against a series of Gram-positive and Gram-negative bacteria. The hydrogels have been used for the entrapment and sustained release of an anticancer drug doxorubicin over 48 h at different pHs (4.8, 7.4, and 8.5) and temperature without the influence of any external stimuli. Such injectable and self-healable hydrogels could be used in various applications in the field of biomedical science.

Nucleopeptide-Coupled Injectable Bioconjugated Guanosine-Quadruplex Hydrogel with Inherent Antibacterial Activity.

The multicomponent reaction-directed self-assembled hydrogels offer the opportunities to fabricate materials with ubiquitous properties which sometimes are not possible to generate from single components. Therefore, multicomponent-derived hydrogels have enormous applications in biomedical fields, and the number of such systems is increasing day by day. Herein, the multicomponent self-assembly techniques have been employed to develop a biomimetic low-molecular-weight G-quadruplex hydrogel under physiological conditions. The bioconjugation of guanosine, 4-formylphenylboronic acid, and cytosine-functionalized nucleopeptide (NP) is important to generate the multicomponent self-assembled dynamic imino-boronate ester-mediated bioconjugated G-quadruplex hydrogels. Using thioflavin T fluorescence assay, powder X-ray diffraction, and circular dichroism spectroscopic techniques, we confirm the existence of a G-quartet-like structure as the key parameter for the formation of nanofibrillar hydrogels. The multicomponent self-assembled G-quadruplex hydrogel possesses excellent inherent antibacterial activity against a broad range of bacterial species. The in vitro cytocompatibility of the synthesized hydrogel was evaluated on MCF-7 and HEK 293T cell lines to study the biocompatibility of the hydrogel. The proposed injectable, biocompatible, and NP-coupled G-quadruplex hydrogel with inherent antibacterial efficiency holds promising importance to prevent localized bacterial infections.

Self-assembled benzoselenadiazole-capped tripeptide hydrogels with inherent in vitro anti-cancer and anti-inflammatory activity.

Self-assembled benzoselenadiazole (BSe)-capped tripeptide based nanofibrillar hydrogels have been developed with inherent anticancer and anti-inflammatory activity.

Bicomponent Coassembled Hydrogel as a Template for Selective Enzymatic Generation of DOPA.

In living organisms, tyrosinase selectively produces l-DOPA from l-tyrosine. Here, a bicomponent hydrogel is used as a template for tyrosinase-catalyzed selective generation of l-DOPA from tyrosine. An amphiphilic molecule 1,5-diaminonaphthalene (DAN) coassembles with 1,3,5-benzenetricarboxylic acid (BTC) to form a self-supporting hydrogel. After alteration of complementary acids, DAN does not coassemble to form a hydrogel. The coassembly mechanism is investigated using spectroscopic techniques. The transmission electron microscopy and scanning electron microscopy images reveal the morphology details. The l-DOPA is kept from being oxidized when the hydrogel is used as a template. The enzymatically synthesized l-DOPA can also be separated from the mixture by easy tuning of the bicomponent coassembly.

A Molecular Link Between Diabetes and Breast Cancer: Therapeutic Potential of Repurposing Incretin-based Therapies for Breast Cancer.

Female breast cancer recently surpassed lung cancer and became the most commonly diagnosed cancer worldwide. As per the recent data from WHO, breast cancer accounts for one out of every 8 cancer cases diagnosed among an estimated 2.3 million new cancer cases. Breast cancer is the most prevailing cancer type among women causing the highest number of cancer-related mortality. It has been estimated that in 2020, 68,5000 women died due to this disease. Breast cancers have varying degrees of molecular heterogeneity; therefore, they are divided into various molecular clinical sub types. Recent reports suggest that type 2 diabetes (one of the common chronic diseases worldwide) is linked to the higher incidence, accelerated progression, and aggressiveness of different cancers; especially breast cancer. Breast cancer is hormone-dependent in nature and has a cross-talk with metabolism. A number of antidiabetic therapies are known to exert beneficial effects on various types of cancers, including breast cancer. However, only a few reports are available on the role of incretin-based antidiabetic therapies in cancer as a whole and in breast cancer in particular. The present review sheds light on the potential of incretin based therapies on breast cancer and explores the plausible underlying mechanisms. Additionally, we have also discussed the sub types of breast cancer as well as the intricate relationship between diabetes and breast cancer.

A platinum nanoparticle doped self-assembled peptide bolaamphiphile hydrogel as an efficient electrocatalyst for the hydrogen evolution reaction.

Noble metal-based nanomaterials have shown great potential for catalytic application with higher selectivity and activity. Owing to their self-assembly properties with various molecular interactions, peptides play an essential role in the controlled synthesis of noble metal-based catalysts with high surface area. In this work, a phenylalanine (F) and tyrosine (Y) based peptide bolaamphiphile is prepared by solution-phase peptide synthesis. The peptide bolaamphiphile readily self-assembles into a hydrogel with a cross-linked nanofibrillar network. The platinum nanoparticles (Pt NPs) are in situ generated within the cross-linked nanofibrillar network of the hydrogel matrix of the peptide bolaamphiphile. Benefiting from the synergistic properties of the Pt nanoparticles doped on three-dimensional fibrous networks, Pt6@hydrogel shows efficient catalytic activity for the electrochemical hydrogen evolution reaction (HER) in 0.5 M H2SO4 solution. The Pt6@hydrogel requires an overpotential of 45 mV at -10 mA cm-2 with a Tafel slope of 52 mV dec-1. The Pt6@hydrogel also shows electrocatalytic activity in basic and neutral pH solutions. The excellent activity and stability of Pt6@hydrogel for the HER shows great potential for energy conversion applications.

Pt Nanoparticles Supported on a Dynamic Boronate Ester-Based G-quadruplex Hydrogel as a Nanoreactor.

Herein, we have reported a dynamic boronic ester mediated guanosine (G) based G-quadruplex hydrogel as an ideal template for in situ and 'green chemical' approach for the synthesis and stabilization of Pt NPs. 11 B NMR and FT-IR spectra reveal the formation of dynamic boronate ester bonds. The TEM images of the G-quadruplex hydrogel reveal entangled three-dimensional (3D) crosslink nanofibrillar networks with average diameter of 20 nm. Similarly, AFM images of the hydrogel show dense nanofibrillar assembly with an average height of 6 nm. The in situ generated Pt NPs have been characterized using TEM and XPS techniques. The average size of the nanofiber supported Pt NPs is 1.5 nm. The Pt NPs embedded G-quadruplex hydrogel shows better mechanical stiffness than the native hydrogel as the storage modulus (G') increases to 2250 Pa from 317.08 Pa after the in situ generation of Pt NPs. Furthermore, G-quadruplex hydrogel supported Pt NPs have been used as a catalytic system for hydrogenation reaction of different aromatic nitro compounds in aqueous medium. The use of G-quadruplex molecular system as a template for the synthesis and stabilization of metal NPs would be an interesting area of research.

Pulse electrodeposited, morphology controlled organic-inorganic nanohybrids as bifunctional electrocatalysts for urea oxidation.

Organic-inorganic nanohybrids with nanoscale architectures and electrocatalytic properties are emerging as a new branch of advanced functional materials. Herein, nanohybrid organic-inorganic nanosheets are grown on carbon paper via a pulse-electrochemical deposition technique. A benzo[2,1,3]selenadiazole-5-carbonyl protected dipeptide BSeFL (BSe = benzoselenadiazole; F = phenylalanine; and L = leucine) cross-linked with Ni2+ ions (Ni-BSeFL) and nickel hydroxide (Ni(OH)2) in a BSeFL/Ni(OH)2 electrode exhibits stable electrocatalytic activity toward urea oxidation. The cross-linked nanosheet morphology of nanohybrids was optimized by controlling the reduction potential during pulse electrodeposition. The BSeFL/Ni(OH)2 (-1.0 V) nanohybrid deposited at -1.0 V provides abundant active sites of Ni3+ with low charge transfer resistance (RCT) and high exchange current density (J0) at the electrocatalytic interface. The nanohybrids with Ni-BSeFL and Ni(OH)2 show low overpotential and superior stability for electrocatalytic urea electro-oxidation. The BSeFL/Ni(OH)2 (-1.0 V) nanohybrid based electrode requires a low potential of 1.30 V (vs. RHE) to acquire a current density of 10 mA cm-2 for the urea oxidation reaction (UOR) in urea containing alkaline solution which is lower than that for water oxidation in alkaline solution (1.49 V vs. RHE). The organic-inorganic nanohybrid BSeFL/Ni(OH)2 (-1.0 V) shows durability over 10 h for oxygen evolution and urea electro-oxidation, thereby confirming the BSeFL/Ni(OH)2 (-1.0 V) nanohybrid-based electrode as an efficient electrocatalyst.

Low molecular weight self-assembling peptide-based materials for cell culture, antimicrobial, anti-inflammatory, wound healing, anticancer, drug delivery, bioimaging and 3D bioprinting applications.

In this review, we have focused on the design and development of low molecular weight self-assembling peptide-based materials for various applications including cell proliferation, tissue engineering, antibacterial, antifungal, anti-inflammatory, anticancer, wound healing, drug delivery, bioimaging and 3D bioprinting. The first part of the review describes about stimuli and various noncovalent interactions, which are the key components of various self-assembly processes for the construction of organized structures. Subsequently, the chemical functionalization of the peptides has been discussed, which is required for the designing of self-assembling peptide-based soft materials. Various low molecular weight self-assembling peptides have been discussed to explain the important structural features for the construction of defined functional nanostructures. Finally, we have discussed various examples of low molecular weight self-assembling peptide-based materials for cell culture, antimicrobial, anti-inflammatory, anticancer, wound healing, drug delivery, bioimaging and 3D bioprinting applications.

A covalent organic polymer as an efficient chemosensor for highly selective H2S detection through proton conduction.

A hydrazide based covalent organic polymer (COP) with pyridine functionalities has been synthesized and used to fabricate an efficient chemosensor for the detection of gaseous H2S at 25 °C through a proton conduction process. The gas sensing behavior of the COP has been measured in a dynamic flow-through resistance measurement system. The COP fabricated sensor shows a lower response time of 9 s with a recovery time of 12 s, when the experiment is performed with a H2S concentration of 200 ppm at 25 °C. It also shows high selectivity to H2S gas compared to other gases such as CO2, NH3, CO and NO2.

Electrodeposited Organic-Inorganic Nanohybrid as Robust Bifunctional Electrocatalyst for Water Splitting.

Rational engineering of novel nanohybrid materials for sustainable and efficient energy conversion has gained extensive research interest. Cross-linked nanosheets of organic-inorganic nanohybrids (BSeF/Ni(OH)2) were fabricated by one-step reductive electrosynthesis and subsequently applied for electrocatalytic water electrolysis. The organic-inorganic nanohybrids consist of benzo[2,1,3]selenadiazole-5-carbonyl phenylalanine (BSeF) cross-linked with nickel ions (Ni-BSeF) and nickel hydroxides (Ni(OH)2), which provide abundant active sites and feasible charge transfer at the electrocatalytic interface. The resulting electrodeposited nanohybrid BSeF/Ni(OH)2 exhibits bifunctional electrocatalytic performance with 240 and 401 mV of overpotential at +100 and -100 mA cm-2 for oxygen evolution reaction (OER) and hydrogen evolution reaction (HER), respectively. The BSeF/Ni(OH)2 offers a longer electrocatalytic activity of 20 h for OER and HER at applied high current densities of +400 and -200 mA cm-2. Coupled with the high OER and HER activity, the two-electrode-based system of BSeF/Ni(OH)2 shows a low cell potential of 1.54 V at 10 mA cm-2. The electrocatalytic performance of Ni-BSeF and Ni(OH)2-based organic-inorganic nanohybrids provides an efficient way to develop a nanohybrid-based catalytic system for energy conversion.

Benzoselenadiazole-Based Conjugated Molecules: Active Switching Layers with Nanofibrous Morphology for Nonvolatile Organic Resistive Memory Devices.

In this work, two symmetrical donor-acceptor-donor (D-A-D) type benzoselenadiazole (BSeD)-based π-conjugated molecules were synthesized and employed as an active switching layer for non-volatile data storage applications. BSeD-based derivatives with different donor units attached through common vinylene linkers showed different electrical and optical properties. 4,7-Di((E)-styryl)benzo[c][2,1,3]selenadiazole (DSBSeD) and 4,7-bis((E)-4-methoxystyryl)benzo[c][2,1,3]selenadiazole (DMBSeD) are sandwiched between gallium-doped ZnO (GZO) and metal aluminum electrodes respectively through solution-processed spin-coating method. The solution-processed nanofibrous switching layer containing the DMBSeD-based memory device showed reliable memory characteristics in terms of write and erase operations with low SET voltage than the random-aggregated DSBSeD-based device. The nanofibrous molecular morphology of switching layer overcomes the interfacial hole transport energy barrier at the interface of the DMBSeD thin-film and the bottom GZO electrode. The memory device GZO/DMBSeD/Al based on nanofibrous switching layers shows switching characteristics at compliance current of 10 mA with Vset =0.79 V and Vreset =-0.55 V. This work will be beneficial for the rational design of advanced next-generation organic memory devices by controlling the nanostructured morphology of active organic switching layer for enhanced charge-transfer phenomenon.

Engineered Dynamic Boronate Ester-Mediated Self-Healable Biocompatible G-Quadruplex Hydrogels for Sustained Release of Vitamins.

Injectable, self-healable, and biocompatible dynamic hydrogels prepared from the molecular self-assembly and reversible covalent bond formation of low-molecular-weight hydrogelators are increasing in the field of drug delivery. Herein, we report the formation of G-quadruplex hydrogels via the multicomponent self-assembly and reversible bond formation between guanosine (G) and 1-naphthaleneboronic acid in the presence of the monovalent cation K+. The cation-templated stacking interaction of G4 quartets and the formation of dynamic cyclic boronate esters are responsible for the construction of dynamic G-quadruplex assembly. The in situ-synthesized dynamic cyclic boronate esters are well characterized by 11B nuclear magnetic resonance and Fourier transform infrared spectroscopy methods. The formation and morphology of the G-quadruplex hydrogel are well supported by several spectroscopic and microscopic techniques. The injectability and self-healing ability of the G-quadruplex hydrogel are also investigated. The in vivo cytotoxicity of the G-quadruplex hydrogel is extensively evaluated over different cell lines (HeLa, MCF-7, and HEK293) to observe the biostability and broad-spectrum biocompatibility of the hydrogel. Further, this injectable, biocompatible G-quadruplex hydrogel has been used for encapsulation and sustained release of two important vitamins (B2 and B12) over 40 h at physiological pH (7.46) and temperature (37 °C) without the influence of any external stimuli.

Evaluation of a Peptide-Based Coassembled Nanofibrous and Thixotropic Hydrogel for Dermal Wound Healing.

The development of a peptide-based coassembled thixotropic hydrogel is a promising biomaterial, which could be used for dermal wound healing application. Cyclodextrins are widely used as biocompatible cyclic oligosaccharides that have hydrophilic exterior and hydrophobic interior for the formation of functional biomaterials. The current work presents a paradigm of a coassembled hydrogel with suitable mechanical strength that exhibits in vivo wound healing efficacy. In this report, we have designed and synthesized an Amoc (9-anthracenemethoxycarbonyl)-capped dipeptide, which self-assembles into a tough and robust hydrogel owing to participation of various noncovalent interactions. The mechanical strength of the self-assembling peptide-based hydrogel is tuned by incorporation of equimolar ß-cyclodextrin (CD), which leads to the formation of a coassembled hydrogel suitable for wound healing application. The coassembled hydrogel exhibits simple syringe injectability and is thixotropic in nature. The nanostructural morphology of the coassembled hydrogel reveals a highly cross-linked and entangled nanofibrillar network. Several spectroscopic data elucidate the presence of noncovalent interactions between CD and peptide, which could be the driving force for the formation of ordered nanostructures. The coassembled hydrogel shows potent antibacterial activity against Gram-positive pathogenic bacteria. In vitro biocompatibility of the coassembled hydrogel has been investigated with the human embryonic kidney (HEK293) and MCF-7 cell lines. Additionally, confocal laser scanning microscopic data show cellular uptake of the coassembled hydrogel with blue fluorescence. Moreover, the in vivo wound healing activity of the coassembled hydrogel has been investigated by the histopathology study. The biochemical parameters such as nitric oxide and collagen contents have been evaluated by Griess and hydroxy proline assays. All the results corroborate the wound healing efficacy of a nanofibrillar antibacterial coassembled hydrogel.

Targeting G-quadruplex DNA with synthetic dendritic peptide: modulation of the proliferation of human cancer cells.

Telomerase, a reverse transcriptase enzyme, is found to over express in most cancer cells. It elongates the telomere region by repeated adding of TTAGGG in the 3'-end and leads to excess cell proliferation which causes cancer. G-quadruplex (G4) formation can inhibit such telomere lengthening. So, stabilization of G4 structure as well as inhibition of telomerase activity is very promising approach in targeted cancer therapy. Herein, the aptitude of a synthetic dendritic peptide, C δ2-(YEE)-E (peptide 1), to target specifically the human telomeric G4 DNA, dAGGG(TTAGGG)3, has been evaluated. Both biochemical and biophysical techniques including gel mobility shift assay, isothermal titration calorimetry and fluorescence spectroscopy have been employed for the purpose. Circular dichroism study reveals that the targeting results an increase in thermal stability of G4 DNA. Interestingly, replacement of N-terminal tyrosine residue of peptide 1 by valine, C δ2-(VEE)-E, (peptide 2) consequences in loss of its G4 DNA targeting ability, although both the peptides exhibit comparable affinity toward double-stranded DNA. Of note, peptide 1 causes cessation of growth of human cancer cells (HeLa and U2OS) and induces apoptosis in vitro. But it has no significant inhibitory effect on the growth of normal human embryonic kidney 293 cells. Mechanistically, Telomeric Repeat Amplification Protocol (TRAP) assay indicates that peptide 1 effectively inhibits the telomerase activity in human cell extracts. Overall, this study demonstrates the usefulness of a synthetic dendritic peptide as an inhibitor of tumor cell growth by inducing apoptosis upon targeting the telomeric G4 DNA.