New Minor Cyclic Peptides from Brachystemma calycinum

From the ethanol extract of the roots of Brachystemma calycinum D. Don, a Chinese folk herb, four new minor cyclic peptides namely brachystemin A, B, C and D (1 - 4) have been isolated. Their structures were established as cyclo (Pro(1)-Phe-Leu-Ala(1)-Thr-Pro(2)-Ala(2)-Gly) (1), cyclo (Pro(1)-Ala-Phe-Trp-Asp-Pro(2)-Leu-Gly) (2), cyclo (Pro(1)-Ile-Gly-Pro(2)-Val-Ala(1)-Ala(2)-Tyr) (3) and cyclo ( Pro-OMet-Trp-Ile-Gly-Ala-Leu-Asp) (4) respectively by means of extensive spectral methods.

Two Cyclic Peptides Produced by the Endophytic Fungus # 2221 from Castaniopsis fissa on the South China Sea Coast

New cyclic peptides 1 and 2 were isolated from the endophytic fungus #2221 fromCastaniopsis fissa on the south China sea coast. By 2D NMR methods and chiral HPLC technique,their structures were elucidated as cyclo (L-Val-L-Leu-L-Val-L-Leu) and cyclo(L-Leu-L-Ala-L-Leu-L-Ala), respectively.

SYNTHESIS OF CYCLIC PEPTIDES USING BBC REAGENT

We report here the synthesis of cyclic peptides using benzotriazolyloxy-bis(pyrrolidino)-carbonium hexafluoro- phosphate(BBC)as a coupling reagent with high yield and speed even in low concentration compared with the other usual coupling reagents.

A COMPARISON OF THE DETERMINATION OF STABILITY CONSTANTS OF COMPLEXES OF Cd(Ⅱ)WITH AMINO ACIDS AND SIMPLE PEPTIDES USING MICRO—pH—METRIC TITRATIONS AND CYCLIC VOLTAMMETRY

This paper reports the determination of stability constants for complexes of Cd(Ⅱ)with Gly, Ala,Val,Asp,Gly—Asp,Asp Gly,Gly—Gly and Gly—Gly—Gly using both micro—pH—metric titra- tions and the application of convolution—deconvolution cyclic voltammetry at 25℃ and I=0.10 mol· dm^(-3)(KNO_3).Stability constants were calculated from pH—metric data using the SUPERQUAD com- puter program and cyclic voltammograms were collected,stored and manipulated using the EG and G CONDECON 300 software.A considerably larger ligand:metal ratio(e,g.50:1)was possible using voltammetry.Evaluation of results from the two techniques suggests that stability constants for the species[CdL_2]and[CdL_3]are reliable when calculated fromvoltammetry while those for[CdL]are more reliable when determined by pH-metric titration.

Two New Cyclic Peptides from Psammosilene tunicoides

From Psammosilene tunicoides W. C. Wu et C. Y Wu, two cyclic octapeptides (namedpsammosilenins A and B) were isolated. Their structures were determined as cyclo(-Pro1-phe1-Pro2-Phe2-Phe3-Ala-Pro3-Leu-) and cyclo(-Pro1-Gly-Phe1-Val-Pro2-Phe2-Thr-Ile) by spectroscopicmethods.

Investigation of the interaction between HIV-1 DNA and cyclic peptides by electrospray ionization mass spectrometry

The interaction between HIV-1 DNA and five cyclic peptides （CP1-CP5） was investigated using electrospray ionization mass spectrometry （ESI-MS）. It revealed that CP1 [c（Ala-Tyr-Leu-Ala-Gly）] and CP4 [c（Pro-D-Tyr-Leu-D-Ala-Gly）] have the higher binding affinity with the duplex DNA among the five cyclic peptides.

Discovery and design of cyclic peptides as dengue virus inhibitors through structure-based molecular docking

Objective:To find potential peptide inhibitors against the NS2B/NS3 protease of DENV which in turn,can inhibit the viral replication inside host cell.Methods:Cyclic peptides were designed having combination of positively charged amino acids using ChemSketch software and were converted to 3D structures.DENV NS3 protein structure was retrieved from Protein Data Bank(PDB)using PDB Id:2FOM.DENV NS3 and cylic peptides were docked using MOE software after structural optimization.Results:Through molecular docking it was revealed that most of the peptides bound deeply in the binding pocket of DENV NS2B/NS3 protease an had interactions with catalytic triad.Peptide 2 successfully blocked the catalytic triad of NS2B/NS3 protease.Peptide 1,,4 and 6 also had potential interactions with active residues of the NS2B/NS3 protease while all other peptides were in close contact with the active sites of NS2B/NS3 protease thus,these peptides can serve as a potential drug candidate to stop viral replication.Conclusions:Thus.it can be concluded from the study that these peptides could serve as important inhibitors to inhibit the viral replication and need further in-vitro investigations to confirm their efficacy.

Cyclic heptapeptides with metal binding properties isolated from the fungus Cadophora malorum from Antarctic soil

The Antarctic fungus Cadophora malorum produces previously undescribed cyclic heptapeptides(cadophorin A and B)containing an anthranilic acid residue.The planar structure of these peptides was determined by high-resolution mass spectrometry combined with extensive 1D and 2D NMR spectroscopy.The absolute configuration of the amino acids was determined by Marfey’s method,with HPLC analysis of FDVA(Nα-(2,4-dinitro-5-fluorphenyl)-l-valinamide)derivatives making use of a PFP column.Remarkably,cadophorin 2 possesses both the uncommon d-Ile and d-allo-Ile in its structure.The peptides have metal binding properties as shown by LCMS with post column addition of metal salt solutions.These results were supported by DFT calculations.

Comparative Study of Disease Suppression on Various Host Plants by <i>Bacillus</i>Cyclic Lipopeptides

In biological controls using Bacillus spp., cyclic lipopeptides play a role as elicitors to induce disease resistance on various host plants. However, it is still unclear the specificity between cyclic lipopeptides and host plants to induce disease resistance. In this study, we aimed to clarify the specificity to induce disease resistance among cyclic lipopeptides on various host plants. Our data clearly showed both cyclic lipopeptides conferred disease suppression on most of host plants, but at different range of cyclic lipopeptide concentration. Our findings contribute to understanding the complex on the specificity of cyclic lipopeptide derived induced disease resistance.

Rh(Ⅲ)-catalyzed late-stage C-H alkenylation and macrolactamization for the synthesis of cyclic peptides with unique Trp(C7)-alkene crosslinks

Heterocycle-braced cyclic peptides have demonstrated enhanced metabolic stability,increased potency and selectivity.Here,we present a rapid synthesis method for constructing Trp(C7)-alkene(E)-crosslinked cyclic peptides with potent anti-proliferative activities against cancer cells,through C-H alkenylation and macrolactamization.This report addresses critical challenges associated with the installation and removal of the directing group N-Piv,configuration selectivity of the olefin,and intramolecular cyclization.No-tably,this method exhibits mild reaction conditions,traceless removal of the directing group,and high configuration selectivity.

Cyclic Beam Direction of Arrival Estimation Method for Ship Propeller Noise

In underwater acoustic applications,the conventional cyclic direction of arrival algorithm faces challenges,including a low signal-to-noise ratio and high bandwidth when compared with modulated frequencies.In response to these issues,this paper introduces a novel,robust,and broadband cyclic beamforming algorithm.The proposed method substitutes the conventional cyclic covariance matrix with the variance of the cyclic covariance matrix as its primary feature.Assuming that the same frequency band shares a common steering vector,the new algorithm achieves superior detection performance for targets with specific modulation frequencies while suppressing interference signals and background noise.Experimental results demonstrate a significant enhancement in the directibity index by 81%and 181%when compared with the traditional Capon beamforming algorithm and the traditional extended wideband spectral cyclic MUSIC(EWSCM)algorithm,respectively.Moreover,the proposed algorithm substantially reduces computational complexity to 1/40th of that of the EWSCM algorithm,employing frequency band statistical averaging and covariance matrix variance.

Molecular and cellular mechanisms of neuroprotection by oligopeptides from snake venoms

Venom snake-derived peptides have multiple biochemical,pharmacological,and toxicological profiles,allowing for the discovery of new medicinal products and therapeutic applications.This review specifically examines the fundamental elements of neuroprotection offered by different oligopeptides derived from snake venom.It also includes a brief evaluation of short peptides that are being considered as potential therapeutic agents.Proline-rich peptides and tryptophyllin family peptides isolated from the crude venom of Viperidae family snakes,specifically Bothrops atrox,Bothrops jararaca,and Bothrops moojeni,have been shown to have pro-survival properties,the ability to reduce oxidative stress,and the ability to promote cell viability and mitochondrial functions.Three significant mechanisms are related to the neuroprotection mediated by snake venom oligopeptides:(1)Activation of the L-arginine metabolite pathway,such as polyamines from ornithine metabolism,which reduces N-methyl-D-aspartate(NMDA)-type glutamate receptor activity;(2)Enhancement of cell viability by activating the nerve growth factor-signaling pathway;and(3)Activation of the Muscarinic acetylcholine receptor subtype M1(mAChR-M1).These small peptides show promise as neuroprotective agents against a variety of neurodegenerative disorders.

Novel umami peptides from two Termitomyces mushrooms and molecular docking to the taste receptor T1R1/T1R3

Wild edible Termitomyces mushrooms are popular in Southwest China and umami is important flavor qualities of edible mushrooms.This study aimed to understand the umami taste of Termitomyces intermedius and Termitomyces aff.bulborhizus.Ten umami peptides from aqueous extracts were separated using a Sephadex G-15 gel filtration chromatography.The intense umami fraction was evaluated by both sensory evaluation and electronic tongue.They were identified as KLNDAQAPK,DSTDEKFLR,VGKGAHLSGEH,MLKKKKLA,SLGFGGPPGY,TVATFSSSTKPDD,AMDDDEADLLLLAM,VEDEDEKPKEK,SPEEKKEEET and PEGADKPNK.Seven peptides,except VEDEDEKPKEK,SPEEKKEEET and PEGADKPNK were selectively synthesized to verify their taste characteristics.All these 10 peptides had umami or salt taste.The 10 peptides were conducted by molecular docking to study their interaction with identified peptides and the umami taste receptor T1R1/T1R3.All these 10 peptides perfectly docked the active residues in the T1R3 subunit.Our results provide theoretical basis for the umami taste and address the umami mechanism of two wild edible Termitomyces mushrooms.

Mechanical responses of anchoring structure under triaxial cyclic loading

Dynamic load on anchoring structures(AS)within deep roadways can result in cumulative damage and failure.This study develops an experimental device designed to test AS under triaxial loads.The device enables the investigation of the mechanical response,failure mode,instability assessment criteria,and anchorage effect of AS subjected to combined cyclic dynamic-static triaxial stress paths.The results show that the peak bearing strength is positively correlated with the anchoring matrix strength,anchorage length,and edgewise compressive strength.The bearing capacity decreases significantly when the anchorage direction is severely inclined.The free face failure modes are typically transverse cracking,concave fracturing,V-shaped slipping and detachment,and spallation detachment.Besides,when the anchoring matrix strength and the anchorage length decrease while the edgewise compressive strength,loading rate,and anchorage inclination angle increase,the failure intensity rises.Instability is determined by a negative tangent modulus of the displacement-strength curve or the continued deformation increase against the general downward trend.Under cyclic loads,the driving force that breaks the rock mass along the normal vector and the rigidity of the AS are the two factors that determine roadway stability.Finally,a control measure for surrounding rock stability is proposed to reduce the internal driving force via a pressure relief method and improve the rigidity of the AS by full-length anchorage and grouting modification.

Three novel umami peptides derived from the alcohol extract of the Pacific oyster(Crassostrea gigas):identification,characterizations and interactions with T1R1/T1R3 taste receptors

Oyster(Crassostrea gigas),the main ingredient of oyster sauce,has a strong umami taste.In this study,three potential umami peptides,FLNQDEEAR(FR-9),FNKEE(FE-5),and EEFLK(EK-5),were identified and screened from the alcoholic extracts of the oyster using nano-HPLC-MS/MS analysis,i Umami-Scoring Card Method(i Umami-SCM)database and molecular docking(MD).Sensory evaluation and electronic tongue analysis were further used to confirm their tastes.The threshold of the three peptides ranged from 0.38 to 0.55 mg/m L.MD with umami receptors T1R1/T1R3 indicated that the electrostatic interaction and hydrogen bond interaction were the main forces involved.Besides,the Phe592 and Gln853 of T1R3 were the primary docking site for MD and played an important role in umami intensity.Peptides with two Glu residues at the terminus had stronger umami,especially at the C-terminus.These results contribute to the understanding of umami peptides in oysters and the interaction mechanism between umami peptides and umami receptors.

Damage evolution of rock-encased-backfill structure under stepwise cyclic triaxial loading

Rock-encased-backfill(RB)structures are common in underground mining,for example in the cut-andfill and stoping methods.To understand the effects of cyclic excavation and blasting activities on the damage of these RB structures,a series of triaxial stepwise-increasing-amplitude cyclic loading experiments was conducted with cylindrical RB specimens(rock on outside,backfill on inside)with different volume fractions of rock(VF=0.48,0.61,0.73,and 0.84),confining pressures(0,6,9,and 12 MPa),and cyclic loading rates(200,300,400,and 500 N/s).The damage evolution and meso-crack formation during the cyclic tests were analyzed with results from stress-strain hysteresis loops,acoustic emission events,and post-failure X-ray 3D fracture morphology.The results showed significant differences between cyclic and monotonic loadings of RB specimens,particularly with regard to the generation of shear microcracks,the development of stress memory and strain hardening,and the contact forces and associated friction that develops along the rock-backfill interface.One important finding is that as a function of the number of cycles,the elastic strain increases linearly and the dissipated energy increases exponentially.Also,compared with monotonic loading,the cyclic strain hardening characteristics are more sensitive to rising confining pressures during the initial compaction stage.Another finding is that compared with monotonic loading,more shear microcracks are generated during every reloading stage,but these microcracks tend to be dispersed and lessen the likelihood of large shear fracture formation.The transition from elastic to plastic behavior varies depending on the parameters of each test(confinement,volume fraction,and cyclic rate),and an interesting finding was that the transformation to plastic behavior is significantly lower under the conditions of 0.73 rock volume fraction,400 N/s cyclic loading rate,and 9 MPa confinement.All the findings have important practical implications on the ability of backfill to support underground excavations.

Andrias davidianus bone peptides alleviates hyperuricemia-induced kidney damage in vitro and in vivo

Hyperuricemia(HUA)is a vital risk factor for chronic kidney diseases(CKD)and development of functional foods capable of protecting CKD is of importance.This paper aimed to explore the amelioration effects and mechanism of Andrias davidianus bone peptides(ADBP)on HUA-induced kidney damage.In the present study,we generated the standard ADBP which contained high hydrophobic amino acid and low molecular peptide contents.In vitro results found that ADBP protected uric acid(UA)-induced HK-2 cells from damage by modulating urate transporters and antioxidant defense.In vivo results indicated that ADBP effectively ameliorated renal injury in HUA-induced CKD mice,evidenced by a remarkable decrease in serum UA,creatinine and blood urea nitrogen,improving kidney UA excretion,antioxidant defense and histological kidney deterioration.Metabolomic analysis highlighted 14 metabolites that could be selected as potential biomarkers and attributed to the amelioration effects of ADBP on CKD mice kidney dysfunction.Intriguingly,ADBP restored the gut microbiome homeostasis in CKD mice,especially with respect to the elevated helpful microbial abundance,and the decreased harmful bacterial abundance.This study demonstrated that ADBP displayed great nephroprotective effects,and has great promise as a food or functional food ingredient for the prevention and treatment of HUA-induced CKD.

Liquefaction susceptibility and deformation characteristics of saturated coral sandy soils subjected to cyclic loadings-a critical review

Coral sandy soils widely exist in coral island reefs and seashores in tropical and subtropical regions.Due to the unique marine depositional environment of coral sandy soils,the engineering characteristics and responses of these soils subjected to monotonic and cyclic loadings have been a subject of intense interest among the geotechnical and earthquake engineering communities.This paper critically reviews the progress of experimental investigations on the undrained behavior of coral sandy soils under monotonic and cyclic loadings over the last three decades.The focus of coverage includes the contractive-dilative behavior,the pattern of excess pore-water pressure(EPWP)generation and the liquefaction mechanism and liquefaction resistance,the small-strain shear modulus and strain-dependent shear modulus and damping,the cyclic softening feature,and the anisotropic characteristics of undrained responses of saturated coral sandy soils.In particular,the advances made in the past decades are reviewed from the following aspects:(1)the characterization of factors that impact the mechanism and patterns of EPWP build-up;(2)the identification of liquefaction triggering in terms of the apparent viscosity and the average flow coefficient;(3)the establishment of the invariable form of strain-based,stress-based,or energy-based EPWP ratio formulas and the unique relationship between the new proxy of liquefaction resistance and the number of cycles required to reach liquefaction;(4)the establishment of the invariable form of the predictive formulas of small strain modulus and strain-dependent shear modulus;and(5)the investigation on the effects of stress-induced anisotropy on liquefaction susceptibility and dynamic deformation characteristics.Insights gained through the critical review of these advances in the past decades offer a perspective for future research to further resolve the fundamental issues concerning the liquefaction mechanism and responses of coral sandy sites subjected to cyclic loadings associated with seismic events in marine environments.

Cyclic shear behavior of en-echelon joints under constant normal stiffness conditions

To reveal the mechanism of shear failure of en-echelon joints under cyclic loading,such as during earthquakes,we conducted a series of cyclic shear tests of en-echelon joints under constant normal stiffness(CNS)conditions.We analyzed the evolution of shear stress,normal stress,stress path,dilatancy characteristics,and friction coefficient and revealed the failure mechanisms of en-echelon joints at different angles.The results show that the cyclic shear behavior of the en-echelon joints is closely related to the joint angle,with the shear strength at a positive angle exceeding that at a negative angle during shear cycles.As the number of cycles increases,the shear strength decreases rapidly,and the difference between the varying angles gradually decreases.Dilation occurs in the early shear cycles(1 and 2),while contraction is the main feature in later cycles(310).The friction coefficient decreases with the number of cycles and exhibits a more significant sensitivity to joint angles than shear cycles.The joint angle determines the asperities on the rupture surfaces and the block size,and thus determines the subsequent shear failure mode(block crushing and asperity degradation).At positive angles,block size is more greater and asperities on the rupture surface are smaller than at nonpositive angles.Therefore,the cyclic shear behavior is controlled by block crushing at positive angles and asperity degradation at negative angles.

MiR-107-3p/Atp6v0e1 contributes to protective effects of two selenium-containing peptides,TSeMMM and SeMDPGQQ on lead-induced neurotoxicity

Two selenium(Se)-containing peptides from Se-enriched rice,TSeMMM and SeMDPGQQ,possess neuroprotective potency against lead(Pb2+)-induced cytotoxicity.However,the crosstalk between mRNA and microRNAs(miRNA)involved in the neuroprotection mechanism remains to be elucidated.In this study,RNA-sequencing and miRNA-sequencing were used to independently identify differentially expressed mRNAs and small RNAs profiles in Pb^(2+)-treated primary fetal rat cortical neurons and then the correlated miRNA-mRNA target pairs were obtained.It was found that 34 mRNAs related to oxidative phosphorylation could be reversed by pretreatment of TSeMMM and SeMDPGQQ.The protective effect of TSeMMM and SeMDPGQQ was mediated by upregulation of miR-107-3p,which downregulates the ATPase H+transporting V0 subunit e1(Atp6v0e1)mRNA level.A zebrafish model was applied to verify the relevance between the targeted mRNA and miRNA by real-time quantitative PCR.The results indicated that miR-107-3p was a potential therapeutic target to achieve neuroprotection of Se-containing peptides via stimulation of Atp6v0e1.