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![Scheme 4. Assembly of doxorubicin (DOX) and 6-mercaptopurine (6-MP) dually loaded polypeptide/gold composite nanoparticles. Source: Wu et al. 2016 [58]. Reproduced with permission of American Chemical Society.](publication/320338546/figure/fig4/AS:669690925948940@1536678167542/Scheme-4-Assembly-of-doxorubicin-DOX-and-6-mercaptopurine-6-MP-dually-loaded.png)
Scheme 4. Assembly of doxorubicin (DOX) and 6-mercaptopurine (6-MP) dually loaded polypeptide/gold composite nanoparticles. Source: Wu et al. 2016 [58]. Reproduced with permission of American Chemical Society.
Source publication
The redox capacity, as well as the aurophilicity of the terminal thiol side groups, in poly(Cysteine) lend a unique characteristic to this poly(amino acid) or polypeptide. There are two major application fields for this polymer: (i) biomedical applications in drug delivery and surface modification of biomedical devices and (ii) as coating for elect...
Citations
... It is obvious from the Raman spectra (Fig. 5) that a sharp band appears at 497 cm −1 (S-S stretching) and absence of band at 2490-2580 cm −1 (S-H stretching) conforms the formation of S-S bond during electropolymerisation. [42][43][44] Oxidation and reduction peaks at around 0.6-0.9 V, 1.4-1.5 V and -0.6 V can be observed even from the first scan of LCys and LCys-MES electropolymerisation on GCE. ...
Apart from the significant physiological roles of hormones and purine metabolites in higher level living organisms, these biomolecules act as recognised biomarkers for early disease detection and its periodical monitoring. Here we detail the development of a voltammetric sensor based on a copolymer of [L-Cystein (LCys) and 2-(N-morpholino)ethanesulfonic acid (MES)] modified glassy carbon electrode for the selective and sensitive determination of Epinephrine (EP), Uric acid (UA), Xanthine (XA), and Hypoxanthine (HX) individually as well as simultaneously. Different perspectives of electrocopolymer formation and involved reaction mechanisms have been investigated and substantiated via Cyclic voltammetry, ATR and Raman spectroscopy. This copolymer modification enables the formation of well-defined peaks for the analytes and under optimised conditions, the designed sensor possess wide linear range with limit of detection of 9.22×10-7 M, 5.147×10-7 M, 1.260×10-7 M, and 2.406×10-7 M for EP, UA, XA, and HX, respectively. Scan rate studies were well employed to derive the mechanistic aspects behind the electrooxidation reactions. The credibility in measurements were validated via repeatability, reproducibility, and stability studies. Also, the feasibility of the proposed sensor was examined in real samples and the results obtained were validated via traditional analytical techniques which demonstrates its practical utility in real time monitoring.
... At lower pH, the negative peak at 196 nm in combination with the positive peak at 218 nm are characteristic of the random coil structure. typical conformation of the free and protected PCys [49]. The terpolymer PEO-b-P(tBM-L-Cys)5-b-P(His)40 (Figure 1a) at pH = 7.4 exhibits a mixed structure of β-turn and β-sheet, which is attributed to both the PHis and PCys moieties. ...
... At these terpolymers, the absorption of the PHis block dominates and overlaps the absorbance of the β-sheet conformation of the protected PCys block. However, in some cases, the secondary structure of the β-sheet is evident, which is the typical conformation of the free and protected PCys [49]. The terpolymer PEO-b-P(tBM-L-Cys) 5 -b-P(His) 40 (Figure 1a) at pH = 7.4 exhibits a mixed structure of β-turn and β-sheet, which is attributed to both the PHis and PCys moieties. ...
Τhe synthesis of a series of novel hybrid block copolypeptides based on poly(ethylene oxide) (PEO), poly(l-histidine) (PHis) and poly(l-cysteine) (PCys) is presented. The synthesis of the terpolymers was achieved through a ring-opening polymerization (ROP) of the corresponding protected N-carboxy anhydrides of Nim-Trityl-l-histidine and S-tert-butyl-l-cysteine, using an end-amine-functionalized poly(ethylene oxide) (mPEO-NH2) as macroinitiator, followed by the deprotection of the polypeptidic blocks. The topology of PCys was either the middle block, the end block or was randomly distributed along the PHis chain. These amphiphilic hybrid copolypeptides assemble in aqueous media to form micellar structures, comprised of an outer hydrophilic corona of PEO chains, and a pH- and redox-responsive hydrophobic layer based on PHis and PCys. Due to the presence of the thiol groups of PCys, a crosslinking process was achieved further stabilizing the nanoparticles (NPs) formed. Dynamic light scattering (DLS), static light scattering (SLS) and transmission electron microscopy (TEM) were utilized to obtain the structure of the NPs. Moreover, the pH and redox responsiveness in the presence of the reductive tripeptide of glutathione (GSH) was investigated at the empty as well as the loaded NPs. The ability of the synthesized polymers to mimic natural proteins was examined by Circular Dichroism (CD), while the study of zeta potential revealed the “stealth” properties of NPs. The anticancer drug doxorubicin (DOX) was efficiently encapsulated in the hydrophobic core of the nanostructures and released under pH and redox conditions that simulate the healthy and cancer tissue environment. It was found that the topology of PCys significantly altered the structure as well as the release profile of the NPs. Finally, in vitro cytotoxicity assay of the DOX-loaded NPs against three different breast cancer cell lines showed that the nanocarriers exhibited similar or slightly better activity as compared to the free drug, rendering these novel NPs very promising materials for drug delivery applications.
... For example, polymers prepared from amino acids have been applied as carriers for nano-vaccines, bioimaging, cancer therapy, and targeted drug delivery. The advantages of utilizing them as carriers for drugs are their controlled release at the intended site, targeted drug delivery, and biodegradable to nontoxic species [4][5][6][7][8][9][10]. ...
Amino acid monomeric units can contribute significantly to a biomass-based and sustainable material because their biomass origin polymers composed of amino acids as in their backbone are biocompatible materials with unique physical properties. In this study, we developed a novel reduction and pH-sensitive poly(disulfide-amide) nanoparticles based on cystine amino acid loaded with doxorubicin (DOX) [(DOX/Cys-PA) NPS] as a fascinating class of nanocarriers that can be applied for targeting anticancer DOX drug delivery. The particle size of (DOX/Cys-PA) NPS with a size range between 200 and 250 nm and parent loading of 12% was prepared using the ionic gelation method by adding FeCl3 polyanion chelating agent, Fe³⁺ form cross-link between the polymer chain. As a result, a characteristic peak for iron appears in XRD analysis. Furthermore, the disulfide linkages enhance the (DOX/Cys-PA) NPS degradability by glutathione (GSH), and the chelating bond of Fe³⁺ enhances the response to pH change. Consequently, in vitro release of DOX at pH 7.4 demonstrates relative stability of the (DOX/Cys-PA) NPS in the bloodstream (pH 7.4) and rapid release of the DOX inside endosomes (pH 5.8 and 0.1 M GSH) of tumor cells.
Graphical Abstract
... Figure 1b and 1c indicates the surface of the PGE after covering by P-L-Cys. As expected, a layer of polymer without pores uniformly distributed on the surface of the electrode [54], indicating the electropolymerization of L-Cys is performed correctly on the surface of the bare electrode. In Fig. 1d, Fe 3 O 4 in the form of fine spherical grains disperses on the surface of the electrode modified with P-L-Cys. ...
Cost-effective simultaneous determination of mercury, copper and cadmium ions was performed by differential pulse anodic stripping voltammetry (DPASV) using a pencil graphite electrode (PGE) modified with poly-L-cysteine (P-L-Cys) and Fe3O4 nanoparticles. Electropolymerization of L-cysteine was performed by cyclic voltammetry (CV) through applying different cycles. Also, Fe3O4 was deposited in a single step by applying a constant potential on the electrode surface in the presence of ferric nitrate. To enhance the sensitivity of measurement, several parameters such as monomer concentration, scan rate, number of cycles in electropolymerization, ferric nitrate concentration, Fe3O4 electrodeposition potential and time, and pH of the sample solution were optimized. The surface morphology of the modified electrode was examined by SEM and FTIR. Electrochemical impedance spectroscopy was conducted to investigate the impedance of the electrode surface. The linear ranges for cadmium, copper and mercury were 0.001‒2500, 0.0002‒3600 and 0.0001‒2500 nM with detection limits of 6.4 × 10–13, 1.0 × 10–13 and 9.0 × 10–14 M, respectively. The stability and reproducibility of the electrode were investigated. Finally, the modified electrode was applied to determine mercury, copper and cadmium in real samples such as the groundwater, Caspian Sea and Tajan River water.
Graphical abstract
... 54 Of note, in our case, the addition of chaotropic thiourea, freshly purified by vacuum sublimation, did not help to overcome this limitation but solely resulted in homopolymer formation ( Figure S1). 55 Nevertheless, as summarized in Table 1, three sets containing four reactive amphiphilic polypept(o)ides have been prepared successfully. These polymers are characterized by comparable chain lengths of 170 and 200 for hydrophilic pSar and 10 to 44 for the hydrophobic reactive S-ethylsulfonyl-protected blocks. ...
Secondary structure formation differentiates polypeptides from most of the other synthetic polymers, and the transitions from random coils to rod-like α-helices or β-sheets represent an additional parameter to direct self-assembly and the morphology of nanostructures. We investigated the influence of distinct secondary structures on the self-assembly of reactive amphiphilic polypept(o)ides. The individual morphologies can be preserved by core cross-linking via chemoselective disulfide bond formation. A series of thiol-responsive copolymers of racemic polysarcosine-block-poly(S-ethylsulfonyl-dl-cysteine) (pSar-b-p(dl)Cys), enantiopure polysarcosine-block-poly(S-ethylsulfonyl-l-cysteine) (pSar-b-p(l)Cys), and polysarcosine-block-poly(S-ethylsulfonyl-l-homocysteine) (pSar-b-p(l)Hcy) was prepared by N-carboxyanhydride polymerization. The secondary structure of the peptide segment varies from α-helices (pSar-b-p(l)Hcy) to antiparallel β-sheets (pSar-b-p(l)Cys) and disrupted β-sheets (pSar-b-p(dl)Cys). When subjected to nanoprecipitation, copolymers with antiparallel β-sheets display the strongest tendency to self-assemble, whereas disrupted β-sheets hardly induce aggregation. This translates to worm-like micelles, solely spherical micelles, or ellipsoidal structures, as analyzed by atomic force microscopy and cryogenic transmission electron microscopy, which underlines the potential of secondary structure-driven self-assembly of synthetic polypeptides.
... The conserved serine residue in the PSAP motif found among Orthohepevirus isolates is also found in the Pak aHEV sequences, which may be a potential phosphorylation site for MAP kinase [32]. The Nterminal half of Pak aHEV ORF3 is hydrophobic, with a high proportion of cysteine residues (27.5%), which may reinforce ORF3 protein folding in the extracellular environment through disulfide bond formation when HEV virions egress the host cell, and act as metal binding motifs inside the host cell [22,32,33]. Pak aHEV ORF3 sequences contain unique amino acid changes S15 T, A31T, Q35H and G46D compared to other aHEV genotypes. ...
Background:
Avian hepatitis E virus (aHEV) has been associated with hepatitis-splenomegaly syndrome (HSS) in chickens along with asymptomatic subclinical infection in many cases. So far, four genotypes have been described, which cause infection in chickens, specifically in broiler breeders and layer chickens. In the present study, we isolated and identified two novel aHEV strains from the bile of layer chickens in Pakistan evincing clinical symptoms related to HSS.
Methodology:
Histology of liver and spleen tissues was carried out to observe histopathological changes in these tissues. Bile fluid and fecal suspensions were used for viral RNA isolation through MegNA pure and Trizol method which was further used for viral genome detection and characterization by cDNA synthesis and amplification of partial open reading frame (ORF) 1, ORF2 and complete ORF3. The bioinformatics tools; Molecular Evolutionary Genetics Analysis version 6.0 (MEGA 6), Mfold and ProtScale were used for phylogenic analysis, RNA secondary structure prediction and protein hydropathy analysis, respectively.
Results:
Sequencing and phylogenetic analysis on the basis of partial methyltranferase (MeT), helicase (Hel) domain, ORF2 and complete ORF3 sequence suggests these Pakistani aHEV (Pak aHEV) isolates may belong to a Pakistani specific clade. The overall sequence similarity between the Pak aHEV sequences was 98-100%. The ORF1/ORF3 intergenic region contains a conserved cis-reactive element (CRE) and stem-loop structure (SLS). Analysis of the amino acid sequence of ORF3 indicated two hydrophobic domains (HD) and single conserved proline-rich domain (PRD) PREPSAPP (PXXPXXPP) with a single PSAP motif found in C-terminal. Amino acid changes S15 T, A31T, Q35H and G46D unique to the Pak aHEV sequences were found in the N-terminal region of ORF3.
Conclusions:
Our data suggests that Pak aHEV isolates may represent a novel Pakistani clade and high sequence homology to each other support the supposition they may belong to a monophyletic clade circulating in the region around Pakistan. The data presented in this study provide further information for aHEV genetic diversity, genotype mapping, global distribution and epidemiology.
... Thiophilic polymers are known and have been used since 1985 for the purification of immunoglobulins [202][203][204][205][206][207]. Also, polymers having cysteine repeat units can be considered as aurophilic, because of the strong affinity of SH-groups to gold [208]. It should be noted that the term aurophilicity has a different meaning in organic chemistry [209]. ...
Recent developments in synthetic pathways as simple reversible-deactivation radical polymerization (RDRP) techniques and quantitative post-polymerization reactions, most notoriously ‘click’ reactions, leading to segmented copolymers, have broadened the molecular architectures accessible to polymer chemists as a matter of routine. Segments can be blocks, grafted chains, branchings, telechelic end-groups, covalently attached nanoparticles, nanodomains in networks, even sequences of random copolymers, and so on. In this review, we describe the variety of the segmented synthetic copolymers landscape from the point of view of their chemical affinity, or synonymous philicity, in bulk or with their surroundings, such as solvents, permeant gases, and solid surfaces. We focus on recent contributions, current trends, and perspectives regarding polyphilic copolymers, which have, in addition to hydrophilic and lipophilic segments, other philicities, for example, towards solvents, fluorophilic entities, ions, silicones, metals, nanoparticles, and liquid crystalline moieties.
... As far as cysteine-functionalized polymers are concerned, despite the different polymer backbones and synthesis strategies reported in the literature, some of the obtained materials have been described to form micelles showing enhanced cell adhesion or improved drug release properties [54,55]. In addition, the thiol group, which is present in some of the chains populations obtained with our strategy, and the carboxyl group can also be used for the grafting or conjugation of peptides sequences, antibodies, drugs or nanoparticles to obtain biomaterials with improved properties [56,57]. ...
ε-caprolactone (CL) has been enzymatically polymerized using α-amino acids based on sulfur (methionine and cysteine) as (co-)initiators and immobilized lipase B of Candida antarctica (CALB) as biocatalyst. In-depth characterizations allowed determining the corresponding involved mechanisms and the polymers thermal properties. Two synthetic strategies were tested, a first one with direct polymerization of CL with the native amino acids and a second one involving the use of an amino acid with protected functional groups. The first route showed that mainly polycaprolactone (PCL) homopolymer could be obtained and highlighted the lack of reactivity of the unmodified amino acids due to poor solubility and affinity with the lipase active site. The second strategy based on protected cysteine showed higher monomer conversion, with the amino acids acting as (co-)initiators, but their insertion along the PCL chains remained limited to chain endcapping. These results thus showed the possibility to synthesize enzymatically polycaprolactone-based chains bearing amino acids units. Such cysteine endcapped PCL materials could then find application in the biomedical field. Indeed, subsequent functionalization of these polyesters with drugs or bioactive molecules can be obtained, by derivatization of the amino acids, after removal of the protecting group.
Providing the reader with an up-to-date digest of the most important current research carried out in the field, this volume is compiled and written by leading experts from across the globe. It reviews the trends in electrochemical sensing and its applications and touches on research areas from a diverse range, including microbial fuel cells, 3D printing electrodes for energy conversion and electrochemical and electrochromic colour switching in metal complexes and polymers.
Coverage is extensive and will appeal to a broad readership from chemists and biochemists to engineers and materials scientists. The reviews of established and current interests in the field make this book a key reference for researchers in this exciting and developing area.
Poly(amino acids) have advanced characteristics, including unique secondary structure, enzyme degradability, good biocompatibility, and stimuli responsibility, and are suitable as drug delivery nanocarriers for tumor therapy. The isoform structure of poly(amino acids) plays an important role in their antitumor efficacy and should be researched in detail. In this study, two kinds of pH-sensitive isoforms, including α-poly(glutamic acid) (α-PGA) and γ-PGA, were selected and used as nanocarriers to prepare a nanodrug delivery system. According to the preparation results, α-PGA can be used as an ideal drug carrier. Selecting doxorubicin (DOX) as the model drug, an α-PGA/DOX nanoparticle (α-PGA/DOX NPs) with a particle size of 110.4 nm was prepared, and the drug-loading content was 66.2%. α-PGA/DOX NPs presented obvious sustained and pH-dependent release characteristics. The IC50 value of α-PGA/DOX NPs was 1.06 ± 0.77 μg mL−1, decreasing by approximately 8.5 fold in vitro against 4T1 cells after incubation for 48 h. Moreover, α-PGA/DOX NPs enhanced antitumor efficacy in vivo, the tumor inhibition rate was 67.4%, increasing 1.5 fold over DOX injection. α-PGA/DOX NPs also reduced the systemic toxicity and cardiotoxicity of DOX. In sum, α-PGA is a biosafe nanodrug delivery carrier with potential clinical application prospects.
