Amino Acids (Journal)

Current research reports and chronological list of recent articles.


The international scientific journal Amino Acids publishes contributions from all fields of amino acid and protein research: analysis, separation, synthesis, biosynthesis, cross linking amino acids, racemization/enantiomers, modification of amino acids as phosphorylation, methylation, acetylation, glycosylation and nonenzymatic glycosylation, new roles for amino acids in physiology and pathophysiology, biology, amino acid analogues and derivatives, polyamines, radiated amino acids, peptides, stable isotopes and isotopes of amino acids. Applications in medicine, food chemistry, nutrition, gastroenterology, nephrology, neurochemistry, pharmacology, excitatory amino acids are just some of the topics covered.

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Additional research articles see Current Chemistry Research Articles. A magazine with similar content (amino acids) is:

 - Journal of Amino Acids (Hindawi).



Amino Acids (Journal) - Abstracts



Recent advances in synthetic lipopeptides as anti-microbial agents: designs and synthetic approaches

Abstract

Infectious diseases impose serious public health burdens and continue to be a global public health crisis. The treatment of infections caused by multidrug-resistant pathogens is challenging because only a few viable therapeutic options are clinically available. The emergence and risk of drug-resistant superbugs and the dearth of new classes of antibiotics have drawn increasing awareness that we may return to the pre-antibiotic era. To date, lipopeptides have been received considerable attention because of the following properties: They exhibit potent antimicrobial activities against a broad spectrum of pathogens, rapid bactericidal activity and have a different antimicrobial action compared with most of the conventional antibiotics used today and very slow development of drug resistance tendency. In general, lipopeptides can be structurally classified into two parts: a hydrophilic peptide moiety and a hydrophobic fatty acyl chain. To date, a significant amount of design and synthesis of lipopeptides have been done to improve the therapeutic potential of lipopeptides. This review will present the current knowledge and the recent research in design and synthesis of new lipopeptides and their derivatives in the last 5 years.


Datum: 01.10.2017


Purification of angiotensin I-converting enzyme (ACE) inhibitory peptides from casein hydrolysate by IMAC-Ni 2+

Abstract

Casein proteins were hydrolyzed by papain to identify inhibitory peptides of angiotensin I-converting enzyme (ACE). The hydrolysate was fractionized by immobilized metal affinity chromatography (IMAC-Ni2+). The fraction with high ACE inhibitory activity was enriched and further chromatographed on a reverse-phase column to yield four fractions. Among the fractions, the L4 fraction exhibited the highest ACE inhibitory activity and was identified by sequence analysis as Trp-Tyr-Leu-His-Tyr-Ala (WYLHYA), with IC50 value of 16.22 ± 0.83 µM in vitro. This peptide was expected to be applied as an ingredient for preventing hypertension and IMAC-Ni2+ may provide a simple method for purification of ACE inhibitory peptides.


Datum: 01.10.2017


Anti-diabetic actions of esculentin-2CHa(1–30) and its stable analogues in a diet-induced model of obesity-diabetes

Abstract

Actions of esculentin-2CHa(1–30) (GFSSIFRGVAKFASKGLGKDLAKLGVDLVA) and its analogues, ([d-Arg7, d-Lys15, d-Lys23]-esculentin-2CHa(1–30) and [Lys15-octanoate]-esculentin-2CHa(1–30), were evaluated in high-fat fed NIH Swiss mice with impaired glucose tolerance and insulin resistance. Twice-daily i.p. administration of the esculentin-2CHa(1–30) peptides (75 nmol/kg body weight) or exendin-4 (25 nmol/kg) for 28 days reduced body weight, without altering cumulative energy intake. All peptides reduced blood glucose levels by 6–12 mmol/l concomitant with lower plasma insulin levels, with significance evident from day 6. All peptides improved glucose tolerance, insulin sensitivity, blood glucose profile over 24 h and decreased HbA1c to a similar extent as exendin-4. The peptides also reduced high fat diet-induced increases in plasma GLP-1 and glucagon. None of the peptides altered bone mineral density/content or lean mass but decreased fat mass. Islets isolated from peptide-treated mice exhibited improved glucose-, alanine- and GLP-1-stimulated insulin secretion. Islet morphometric analyses revealed that exendin-4 and the esculentin-2CHa(1–30) peptides significantly reduced islet, beta and alpha cell areas compared to high-fat controls. Esculentin-2CHa(1–30) peptides markedly reduced high fat diet-induced increase in beta cell proliferation and apoptosis. Peptide treatments had beneficial effects on expression of islet genes (Ins1, Slc2a2, Pdx1) and skeletal muscle genes involved in insulin action (Slc2a4, Pdk1, Irs1, Akt1). High-fat diet significantly increased LDL cholesterol which was reduced by the acylated esculentin-2CHa(1–30) analogue. Peptide treatments did not alter circulating concentrations of amylase and marker enzymes of liver function, indicating a lack of toxicity. These data indicate that esculentin-2CHa(1–30) and its analogues may be useful for improvement of blood glucose control and weight loss in type 2 diabetes.


Datum: 01.10.2017


Physico-chemical characterization of formulations containing endomorphin-2 derivatives

Abstract

In this study semisolid formulations containing AcYPFF (N-acetyl-Tyr-Pro-Phe-Phe-NH2) tetrapeptide were obtained and characterized in terms of rheology, stability by multiple light scattering and particle size distribution by laser diffraction. Additionally, the release studies of tetrapeptide from formulations obtained were performed. The influence of different factors such as semisolid and membrane type on tetrapeptide release rate was examined. The release experiments of tetrapeptide modified with palmitoyl group (PalmYPFF) were also carried out. The results proved that formulation type and its rheological properties strongly determined the permeation process of the tetrapeptide. The fastest release of tetrapeptide was observed from hydrogel that had the lowest viscosity. The kinetic data of tetrapeptide released from oil-in-water (o/w) and water-in-oil (w/o) emulsions prepared at elevated temperature showed good fit to the Higuchi equation, whereas when AcYPFF was released from oil-in-water (o/w) emulsion prepared with the addition of auto-emulsifier high linearity with Korsmeyer–Peppas model was observed. While when tetrapeptide was released from Hydrogel the most suitable model was the first-order kinetics. It was suggested that mechanism that led to the release of tetrapeptide from all formulations was non-Fickian diffusion transport. The presence of palmitoyl group changed the solubility of tetrapeptide both in formulation and receptor fluid and thus the release rate of active compound was modified.


Datum: 01.10.2017


The African froghopper Ptyelus flavescens (suborder: Cicadomorpha) contains two novel and one known peptides of the adipokinetic hormone (AKH) family: structure, function and comparison with aphid AKH (suborder: Sternorrhyncha)

Abstract

The rationale of “green pesticides” in food security is to use information about endogenous hormones of pest insects to make peptide mimetics that will act against the pest insects to alter their behaviour or physiology, while taking care not to harm beneficial insects or other organisms in the food chain. Such “green” insecticides are designed thus, on the basis of neuropeptide ligand–receptor interaction and it is of paramount interest to have finally a mimetic at hand that is harmful only to pest insects. For this concept to work, one has to identify the ligands in pest and beneficial insects. In this study we investigate adipokinetic hormones (AKHs) from a hemipteran source. The most harmful hemipterans on an economic scale are aphids (Hemiptera: Sternorrhyncha: Aphidoidea) of which the AKH is known. Here we identify the AKH complement of a member of a related suborder, the raintree bug or froghopper Ptyelus flavescens (Hemiptera: Cicadomorpha: Cercopoidea). Identification and sequence elucidation of the adipokinetic peptides of this species was achieved by a heterospecific and conspecific trehalose-mobilizing bioassay, and by liquid chromatography coupled to positive electrospray mass spectrometry (LC–ESI–MS) including tandem MS2 spectra obtained by collision-induced dissociation. High resolution MS was employed to distinguish between Gln and Lys residues in the peptides. Three AKHs are discovered in the raintree bug: an octapeptide (Peram-CAH-I: pEVNFSPNW amide) previously known from cockroaches, and two novel decapeptides (Ptyfl-AKH-I: pEINFSTGWGQ amide and Ptyfl-AKH-II: pEINFSTAWGQ amide). The novel peptides were synthesized and the sequence assignments were unequivocally confirmed by co-elution of synthetic peptides and the natural equivalent and by identical MS data of the two forms. A conspecific bioassay in the froghopper describe the endogenous peptide Ptyfl-AKH-I as hypertrehalosemic. In heterologous bioassays the two novel AKHs induce an increase of circulating carbohydrates in cockroaches: Ptyfl-AKH-I is much more active than Ptyfl-AKH-II. Moreover, if the Ile2 in Ptyfl-AKH-II is replaced with a Leu2 residue, biological activity is further diminished. The current data show that the raintree AKH decapeptides differ by four amino acids from the aphid AKH (Acypi-AKH: pEVNFTPTWGQ amide). Therefore, it may be permissible to use the aphid AKH ligand–receptor pair to develop a “green” insecticide to target aphid metabolism.


Datum: 01.10.2017


Retro analog concept: comparative study on physico-chemical and biological properties of selected antimicrobial peptides

Abstract

Increasing drug resistance of common pathogens urgently needs discovery of new effective molecules. Antimicrobial peptides are believed to be one of the possible solutions of this problem. One of the approaches for improvement of biological properties is reversion of the sequence (retro analog concept). This research is based on investigation of antimicrobial activity against Gram-positive, Gram-negative bacteria, and fungi, hemolysis of erythrocytes, interpretation of the circular dichroism spectra, measurement of counter-ion content, and assessment of the peptide hydrophobicity and self-assembly using reversed-phase chromatography. The experiments were conducted using the following peptides: aurein 1.2, CAMEL, citropin 1.1, omiganan, pexiganan, temporin A, and their retro analogs. Among the compounds studied, only retro omiganan showed an enhanced antimicrobial and a slightly increased hemolytic activity as compared to parent molecule. Moreover, retro pexiganan exhibited high activity towards Klebsiella pneumoniae, whereas pexiganan was in general more or equally active against the rest of tested microorganisms. Furthermore, the determined activity was closely related to the peptide hydrophobicity. In general, the reduced hemolytic activity correlates with lower antimicrobial activity. The tendency to self-association and helicity fraction in SDS seems to be correlated. The normalized RP-HPLC—temperature profiles of citropin 1.1 and aurein 1.2, revealed an enhanced tendency to self-association than that of their retro analogs.


Datum: 01.10.2017


Protein binding hot spots prediction from sequence only by a new ensemble learning method

Abstract

Hot spots are interfacial core areas of binding proteins, which have been applied as targets in drug design. Experimental methods are costly in both time and expense to locate hot spot areas. Recently, in-silicon computational methods have been widely used for hot spot prediction through sequence or structure characterization. As the structural information of proteins is not always solved, and thus hot spot identification from amino acid sequences only is more useful for real-life applications. This work proposes a new sequence-based model that combines physicochemical features with the relative accessible surface area of amino acid sequences for hot spot prediction. The model consists of 83 classifiers involving the IBk (Instance-based k means) algorithm, where instances are encoded by important properties extracted from a total of 544 properties in the AAindex1 (Amino Acid Index) database. Then top-performance classifiers are selected to form an ensemble by a majority voting technique. The ensemble classifier outperforms the state-of-the-art computational methods, yielding an F1 score of 0.80 on the benchmark binding interface database (BID) test set.Availability: http://www2.ahu.edu.cn/pchen/web/HotspotEC.htm.


Datum: 01.10.2017


Stabilization of Angiotensin-(1–7) by key substitution with a cyclic non-natural amino acid

Abstract

Angiotensin-(1–7) [Ang-(1–7)], a heptapeptide hormone of the renin–angiotensin–aldosterone system, is a promising candidate as a treatment for cancer that reflects its anti-proliferative and anti-angiogenic properties. However, the peptide’s therapeutic potential is limited by the short half-life and low bioavailability resulting from rapid enzymatic metabolism by peptidases including angiotensin-converting enzyme (ACE) and dipeptidyl peptidase 3 (DPP 3). We report the facile assembly of three novel Ang-(1–7) analogues by solid-phase peptide synthesis which incorporates the cyclic non-natural δ-amino acid ACCA. The analogues containing the ACCA substitution at the site of ACE cleavage exhibit complete resistance to human ACE, while substitution at the DDP 3 cleavage site provided stability against DPP 3 hydrolysis. Furthermore, the analogues retain the anti-proliferative properties of Ang-(1–7) against the 4T1 and HT-1080 cancer cell lines. These results suggest that ACCA-substituted Ang-(1–7) analogues which show resistance against proteolytic degradation by peptidases known to hydrolyze the native heptapeptide may be novel therapeutics in the treatment of cancer.


Datum: 01.10.2017


Triple serine loop region regulates the aspartate racemase activity of the serine/aspartate racemase family

Abstract

Recently, we cloned and characterized eleven serine and aspartate racemases (SerR and AspR, respectively) from animals. These SerRs and AspRs are not separated by their racemase functions and form a serine/aspartate racemase family cluster based on phylogenetic analysis. Moreover, we have proposed that the AspR-specific triple serine loop region at amino acid positions 150–152 may be responsible for the large AspR activity. In the present study, to test this hypothesis, we prepared and characterized fourteen mutants in this region of animal SerRs and AspRs. The large AspR activity in Acropora and Crassostrea AspR was reduced to <0.04% of wild-type after substitution of the triple serine loop region. Conversely, introducing the triple serine loop region into Acropora, Crassostrea, and Penaeus SerR drastically increased the AspR activity. Those mutants showed similar or higher substrate affinity for aspartate than serine and showed 11–683-fold higher k cat and 28–351-fold higher k cat/K m values for aspartate than serine racemization. Furthermore, we introduced serine residues in all combinations at position 150–152 in mouse SerR. These mutants revealed that a change in the enzyme function from SerR to AspR can be caused by introduction of Ser151 and Ser152, and addition of the third serine residue at position 150 further enhances the enzyme specificity for aspartate due to a decrease in the serine racemase and serine dehydratase activity. Here, we provide convincing evidence that the AspR gene has evolved from the SerR gene by acquisition of the triple serine loop region.


Datum: 01.10.2017


Structure–function relationships of protein–lipopeptide complexes and influence on immunogenicity

Abstract

The lipopeptide, R4Pam2Cys, associates electrostatically with soluble protein antigens and significantly enhances their ability to induce protective humoral and cell-mediated responses. We demonstrate that antibody titers elicited by the antigen ovalbumin (OVA) associated with R4Pam2Cys are higher than those elicited by OVA in the presence of alum and comparable to those elicited by OVA formulated with complete Freund’s adjuvant (CFA). The hierarchy of anti-OVA antibody avidities was CFA > R4Pam2Cys = alum. Each of the three adjuvants facilitated IgG class-switching with significantly more IgG1 elicited by OVA when formulated with R4Pam2Cys. The effects of substituting naturally occurring l-stereoisomers of the cationic residues within R4Pam2Cys with d-stereoisomers revealed that substitution did not affect the ability of R4Pam2Cys to stimulate dendritic cell maturation or its ability to elicit antibody production when used as an adjuvant. Minor detrimental effects were, however, observed in the ensuing CD8+ T cell responses suggesting that the use of d-amino acids affects antigen processing and presentation pathways involved in generation of cell-mediated immunity at least when facilitated through TLR2. Both d- and l-forms were found to be resistant to digestion by trypsin, indicating resistance of the branched structure to protease activity.


Datum: 01.10.2017


Taurine counteracts the neurotoxic effects of streptozotocin-induced diabetes in rats

Abstract

Diabetes is a chronic metabolic disease associated with oxidative stress, damage to biomolecules such as DNA, and neuroinflammation. Taurine, a sulfur-containing amino acid widespread in the brain, has neuroprotective properties that might prevent tissue injury and DNA damage induced by chronic hyperglycemia. We evaluated the effects of chronic taurine treatment on oxidative stress parameters, DNA damage and inflammatory markers in the frontal cortex, and hippocampus of streptozotocin-induced diabetic rats. Diabetic rats displayed increased levels of reactive oxygen species (ROS) and DNA damage in both areas, evidencing the pro-oxidant effects of diabetes in the brain. Moreover, this condition increased levels of several inflammatory mediators, such as IL-6, IL-12, TNF-γ, and IFN-α, more pronouncedly in the hippocampus. Supporting our hypothesis, taurine treatment reduced ROS, DNA damage, and inflammatory cytokine levels, providing evidence of its beneficial effects against genotoxicity and neuroinflammation associated with diabetes. Our data endorse the necessary clinical trials to evaluate the efficacy and safety of taurine supplementation in the prevention and treatment of neurochemical and metabolic alterations related to diabetes.


Datum: 21.09.2017


A review of the relationship between the gut microbiota and amino acid metabolism

Abstract

New evidence has emerged in recent years to suggest a strong link between the human gut microbiota, its metabolites, and various physiological aspects of hosts along with important pathophysiological dimensions of diseases. The research indicates that the gut microbiota can facilitate metabolite production in two ways: first, the resident species of the gut microbiota use the amino acids produced from food or the host as elements for protein synthesis, and second, conversion or fermentation are used to drive nutrient metabolism. Additionally, the gut microbiota can synthesize several nutritionally essential amino acids de novo, which is a potential regulatory factor in amino acid homeostasis. The primary objective of this review is to summarize the current literature relating to the ways in which microbial amino acids contribute to host amino acid homeostasis.


Datum: 20.09.2017


Roles of dietary glycine, proline, and hydroxyproline in collagen synthesis and animal growth

Abstract

Glycine, proline, and hydroxyproline (Hyp) contribute to 57% of total amino acids (AAs) in collagen, which accounts for one-third of proteins in animals. As the most abundant protein in the body, collagen is essential to maintain the normal structure and strength of connective tissue, such as bones, skin, cartilage, and blood vessels. Mammals, birds, and fish can synthesize: (1) glycine from threonine, serine, choline, and Hyp; (2) proline from arginine; and (3) Hyp from proline residues in collagen, in a cell- and tissue-specific manner. In addition, livestock (e.g., pigs, cattle, and sheep) produces proline from glutamine and glutamate in the small intestine, but this pathway is absent from birds and possibly most fish species. Results of the recent studies indicate that endogenous synthesis of glycine, proline, and Hyp is inadequate for maximal growth, collagen production, or feed efficiency in pigs, chickens, and fish. Although glycine, proline and Hyp, and gelatin can be used as feed additives in animal diets, these ingredients except for glycine are relatively expensive, which precludes their inclusion in practical rations. Alternatively, hydrolyzed feather meal (HFM), which contains 9% glycine, 5% Hyp, and 12% proline, holds great promise as a low cost but abundant dietary source of glycine, Hyp, and proline for ruminants and nonruminants. Because HFM is deficient in most AAs, future research efforts should be directed at improving the bioavailability of its AAs and the balance of AAs in HFM-supplemented diets. Finally, HFM may be used as a feed additive to prevent or ameliorate connective tissue disorders in domestic and aquatic animals.


Datum: 20.09.2017


Escherichia coli aggravates endoplasmic reticulum stress and triggers CHOP-dependent apoptosis in weaned pigs

Abstract

Intestinal cells can sense the presence of pathogens and trigger many important signaling pathways to maintain tissue homeostasis and normal function. Escherichia coli and lipopolysaccharides (LPS) are the main pathogenic factors of intestinal disease in pigs. However, the roles of endoplasmic reticulum stress (ERS) and its mediated apoptosis in intestinal malfunction induced by E. coli or LPS remain unclear. In the present study, we aimed to evaluate whether ERS could be activated by E. coli fed to piglets and whether the underlying mechanisms of this disease process could be exploited. Eighteen weaned pigs (21 days old) were randomly assigned to one of two treatment groups (n = 9 per group). After pre-feeding for 1 week, the diets of the piglets in one group were supplemented with E. coli (W25 K, 109 cells kg−1 diet) for 7 days. At the end of the experiment, all piglets were slaughtered to collect jejunum and ileum samples. Western blotting and immunofluorescence experiments were used to determine the expression levels and histological locations of ERS and its downstream signaling proteins. The intestinal porcine epithelial cell line J2 (IPEC-J2) was used as in vitro model to investigate the possible mechanism. The results showed that E. coli supplementation in the diet increased the GRP78 expression in the jejunum and ileum, especially in the jejunal epithelium and ileac germinal center, and elevated the expression levels of CHOP (in both the jejunum and ileum) and caspase-11 (in the ileum), indicating that ERS and CHOP–caspase-11 dependent apoptosis were activated in the porcine small intestine. Moreover, as demonstrated by in vitro experiments, the CHOP inhibitor 4-phenylbutyrate alleviated the damage to IPEC-J2 cells induced by LPS derived from E. coli. Taken together, these data strongly suggest that ERS can be triggered in the small intestine by dietary supplementation with E. coli and that CHOP–caspase-11 dependent apoptosis may play a key role in maintaining normal homeostasis of the intestine in response to pathogenic factors.


Datum: 19.09.2017


Melatonin alters amino acid metabolism and inflammatory responses in colitis mice

Abstract

Inflammatory bowel disease is a chronic inflammatory dysfunction of the gastrointestinal tract. This study explored the hypothesis that melatonin has beneficial functions in the mouse model of colitis induced by dextran sodium sulfate (DSS), with a specific focus on the expression of intestinal inflammatory cytokines and the serum levels of amino acids. The results revealed that mice with melatonin supplementation had a reduction in weight loss and disease index induced by DSS treatment. Melatonin stifled the expression of colonic IL-17 in mice with DSS-induced colitis. Melatonin also lowered the serum levels of Asp, Ser, Met, and Leu (p < 0.05), but increased those of Glu and Cys (p < 0.05). Thus, melatonin treatment is promising and may function as a potential adjuvant therapy to alleviate the clinical symptoms of patients with inflammatory bowel disease.


Datum: 19.09.2017


The role of methionine on metabolism, oxidative stress, and diseases

Abstract

Methionine is an aliphatic, sulfur-containing, essential amino acid, and a precursor of succinyl-CoA, homocysteine, cysteine, creatine, and carnitine. Recent research has demonstrated that methionine can regulate metabolic processes, the innate immune system, and digestive functioning in mammals. It also intervenes in lipid metabolism, activation of endogenous antioxidant enzymes such as methionine sulfoxide reductase A, and the biosynthesis of glutathione to counteract oxidative stress. In addition, methionine restriction prevents altered methionine/transmethylation metabolism, thereby decreasing DNA damage and carcinogenic processes and possibly preventing arterial, neuropsychiatric, and neurodegenerative diseases. This review focuses on the role of methionine in metabolism, oxidative stress, and related diseases.


Datum: 19.09.2017


4-Chloro-3-nitro- N -butylbenzenesulfonamide acts on K V 3.1 channels by an open-channel blocker mechanism

Abstract

The effects of 4-chloro-3-nitro-N-butylbenzenesulfonamide (SMD2) on KV3.1 channels, heterologous expressed in L-929 cells, were studied with the whole cell patch-clamp technique. SMD2 blocks KV3.1 in a reversible and use-dependent manner, with IC50 around 10 µM, and a Hill coefficient around 2. Although the conductance vs. voltage relationship in control condition can be described by a single Boltzmann function, two terms are necessary to describe the data in the presence of SMD2. The activation and deactivation time constants are weakly voltage dependent both for control and in the presence of SMD2. SMD2 does not change the channel selectivity and tail currents show a typical crossover phenomenon. The time course of inactivation has a fast and a slow component, and SMD2 significantly decreased their values. Steady-state inactivation is best described by a Boltzmann equation with V 1/2 (the voltage where the probability to find the channels in the inactivated state is 50%) and K (slope factor) equals to −22.9 ± 1.5 mV and 5.3 ± 0.9 mV for control, and −30.3 ± 1.3 mV and 6 ± 0.8 mV for SMD2, respectively. The action of SMD2 is enhanced by high frequency stimulation, and by the time the channel stays open. Taken together, our results suggest that SMD2 blocks the open conformation of KV3.1. From a pharmacological and therapeutic point of view, N-alkylsulfonamides may constitute a new class of pharmacological modulators of KV3.1.


Datum: 12.09.2017


Identification and characterization of novel broad-spectrum amino acid racemases from Escherichia coli and Bacillus subtilis

Abstract

The peptidoglycan layer of the bacterial cell wall typically contains d-alanine (d-Ala) and d-glutamic acid (d-Glu), and also various non-canonical d-amino acids that have been linked to peptidoglycan remodeling, inhibition of biofilm formation, and triggering of biofilm disassembly. Bacteria produce d-amino acids when adapting to environmental changes as a common survival strategy. In our previous study, we detected non-canonical d-amino acids in Escherichia coli grown in minimal medium. However, the biosynthetic pathways of non-canonical d-amino acids remain poorly understood. In the present study, we identified amino acid racemases in E. coli MG1655 (YgeA) and Bacillus subtilis (RacX) that produce non-canonical d-amino acids other than d-Ala and d-Glu. We characterized their enzymatic properties, and both displayed broad substrate specificity but low catalytic activity. YgeA preferentially catalyzes the racemization of homoserine, while RacX preferentially racemizes arginine, lysine, and ornithine. RacX is dimeric, and appears not to require pyridoxal 5′-phosphate (PLP) as a coenzyme as is the case with YgeA. To our knowledge, this is the first report on PLP-independent amino acid racemases possessing broad substrate specificity in E. coli and B. subtilis.


Datum: 11.09.2017


Targeting cancer-specific glycans by cyclic peptide lectinomimics

Abstract

The transformation from normal to malignant phenotype in human cancers is associated with aberrant cell-surface glycosylation. Thus, targeting glycosylation changes in cancer is likely to provide not only better insight into the roles of carbohydrates in biological systems, but also facilitate the development of new molecular probes for bioanalytical and biomedical applications. In the reported study, we have synthesized lectinomimics based on odorranalectin 1; the smallest lectin-like cyclic peptide isolated from the frog Odorrana grahami skin, and assessed the ability of these peptides to bind specific carbohydrates on molecular and cellular levels. In addition, we have shown that the disulfide bond found in 1 can be replaced with a lactam bridge. However, the orientation of the lactam bridge, peptides 2 and 3, influenced cyclic peptide‘s conformation and thus these peptides’ ability to bind carbohydrates. Naturally occurring 1 and its analog 3 that adopt similar conformation in water bind preferentially l-fucose, and to a lesser degree d-galactose and N-acetyl-d-galactosamine, typically found within the mucin O-glycan core structures. In cell-based assays, peptides 1 and 3 showed a similar binding profile to Aleuria aurantia lectin and these two peptides inhibited the migration of metastatic breast cancer cell lines in a Transwell assay. Altogether, the reported data demonstrate the feasibility of designing lectinomimics based on cyclic peptides.


Datum: 11.09.2017


Pro-apoptotic cationic host defense peptides rich in lysine or arginine to reverse drug resistance by disrupting tumor cell membrane

Abstract

Host defense peptides have been demonstrated to exhibit prominent advantages in cancer therapy with selective binding ability toward tumor cells via electrostatic attractions, which can overcome the limitations of traditional chemotherapy drugs, such as toxicity on non-malignant cells and the emergence of drug resistance. In this work, we redesigned and constructed a series of cationic peptides by inserting hydrophobic residues into hydrophilic surface or replacing lysine (K) with arginine (R), based on the experience from the preliminary work of host defense peptide B1. In-depth studies demonstrated that the engineered peptides exhibited more potent anti-cancer activity against various cancer cell lines and much lower toxicity to normal cells compared with B1. Further investigation revealed that compounds I-3 and I-7 could act on cancer cell membranes and subsequently alter the permeability, which facilitated obvious pro-apoptotic activity in paclitaxel-resistant cell line (MCF-7/Taxol). The result of mitochondrial membrane potential assay (ΔΨm) demonstrated that the peptides induced ΔΨm dissipation and mitochondrial depolarization. The caspase-3 cellular activity assay showed that the anti-cancer activity of peptides functioned via caspase-3-dependent apoptosis. The study yielded compound I-7 with superior properties for antineoplastic activity in comparison to B1, which makes it a promising potential candidate for cancer therapy.


Datum: 01.09.2017






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