To relieve itch and pain without undesirable side effects, chemists put a kill switch on capsaicin

To relieve itch and pain without worrisome side effects, chemists put a kill switch on capsaicin

Massive clinical trial including developing nations demonstrates carbetocin is no less effective or safe than oxytocin

Indianapolis police arrested a man on Saturday near the location of the fatal police shooting of Dreasjon "Sean" Reed days earlier.

Demonstrators describe an arrest and pepper ball use by IMPD during a protest over the death of Dreasjon Reed near 62nd Street and Michigan Road.

Indianapolis police arrested a man on Saturday near the location of the fatal police shooting of Dreasjon "Sean" Reed days earlier.

The TVS Scooty Pep+ surprisingly has got more power in the BS6 era while the kerb weight still stays the same; fantastic recipe for good performance.

BS-VI Honda SP125 Review: Honda's second BS6 compliant two-wheeler not only is now more fuel-efficient and cleaner for the environment, but it also offers several new features. We rode it around the streets of Mumbai to find out more.

Cathy Yan has followed in Patty Jenkins’ footsteps by directing a DC movie.

Several dozen gathered at the intersection of 62nd Street and Michigan Road in Indianapolis on Saturday, where a police officer fatally shot Dreasjon 'Sean' Reed, 21, on Wednesday.

Manchester City boss Pep Guardiola has revealed Aymeric Laporte will be out of action for 'five to six months' with a serious knee injury sustained during the club's victory over Brighton.

The new deadline format would allow Premier League sides to to buy from, as well as sell to, foreign teams up until the end of August. Domestic deals would have to be done before the season.

Sterling has enjoyed a blistering start to the season, scoring eight goals in seven games for Manchester City and England, earning him comparisions with some of the game's greats.

The Bundesliga is restarting on May 16 and players will be isolated in hotels before matches. Among the rules for the Bundesligas return are detailed instructions for coaches.

On Mother's Day 2020, singer Anushka Manchanda has recorded a peppy and upbeat ode to mothers all across the globe, aptly titled 'Thanks Maa.'

Dietary capsaicin elicits proteomic shifts in rats fed a high-fat diet.

Crystals of the dimethyl sulfoxide (DMSO) solvate of [1–9-NαC]-linusorb B3 (Cyclo­linopeptide A; CLP-A; C57H84N9O9·C2H6OS), a cyclic polypeptide were obtained following peptide extraction and purification from flaxseed oil. There are four intramolecular N—H⋯O hydrogen bonds. In the crystal, the mol­ecules are linked in chains along the a axis by N—H⋯O hydrogen bonds. Each DMSO O atom accepts a hydrogen bond from an NH group at the Phe6 location in the CLP-A mol­ecule.

A peptide biphenyl hybrid compound {systematic name: dimethyl 2,2'-[((2S,2'S)-2,2'-{[(2S,2'S)-1,1'-([1,1'-biphen­yl]-2,2'-dicarbon­yl)bis­(pyrrolidine-1,2-diyl-2-carbon­yl)]bis­(aza­nedi­yl)}bis­(3-phenyl­propano­yl))bis­(aza­nedi­yl)](2S,2'S)-dipropionate hemihydrate}, C50H56N6O10·0.5H2O, was prepared by coupling of [1,1'-biphen­yl]-2,2'-dicarbonyl dichloride, tri­ethyl­amine and the tripeptide Pro–Phe–Ala in CH2Cl2 at 273 K under an N2 atmosphere. In the crystal, the asymmetric unit contains the peptide biphenyl hybrid accompanied by one-half of a water mol­ecule. A C atom of one of the proline rings is disordered between two positions in a 0.746 (11):0.254 (11) ratio. An important structural aspect of peptide compounds is their capacity to self-associate mediated by inter­molecular and intra­molecular hydrogen bonding. This characteristic can be useful in understanding the inter­actions between peptides and biomacromolecular targets, as well as to explain peptide properties.

Indanomycin is biosynthesized by a hybrid nonribosomal peptide synthase/polyketide synthase (NRPS/PKS) followed by a number of `tailoring' steps to form the two ring systems that are present in the mature product. It had previously been hypothesized that the indane ring of indanomycin was formed by the action of IdmH using a Diels–Alder reaction. Here, the crystal structure of a selenomethionine-labelled truncated form of IdmH (IdmH-Δ99–107) was solved using single-wavelength anomalous dispersion (SAD) phasing. This truncated variant allows consistent and easy crystallization, but importantly the structure was used as a search model in molecular replacement, allowing the full-length IdmH structure to be determined to 2.7 Å resolution. IdmH is a homodimer, with the individual protomers consisting of an α+β barrel. Each protomer contains a deep hydrophobic pocket which is proposed to constitute the active site of the enzyme. To investigate the reaction catalysed by IdmH, 88% of the backbone NMR resonances were assigned, and using chemical shift perturbation of [15N]-labelled IdmH it was demonstrated that indanomycin binds in the active-site pocket. Finally, combined quantum mechanical/molecular mechanical (QM/MM) modelling of the IdmH reaction shows that the active site of the enzyme provides an appropriate environment to promote indane-ring formation, supporting the assignment of IdmH as the key Diels–Alderase catalysing the final step in the biosynthesis of indanomycin through a similar mechanism to other recently characterized Diels–Alderases involved in polyketide-tailoring reactions. An animated Interactive 3D Complement (I3DC) is available in Proteopedia at https://proteopedia.org/w/Journal:IUCrJ:S2052252519012399.

Tannerella forsythia is an oral dysbiotic periodontopathogen involved in severe human periodontal disease. As part of its virulence factor armamentarium, at the site of colonization it secretes mirolysin, a metallopeptidase of the unicellular pappalysin family, as a zymogen that is proteolytically auto-activated extracellularly at the Ser54–Arg55 bond. Crystal structures of the catalytically impaired promirolysin point mutant E225A at 1.4 and 1.6 Å revealed that latency is exerted by an N-terminal 34-residue pro-segment that shields the front surface of the 274-residue catalytic domain, thus preventing substrate access. The catalytic domain conforms to the metzincin clan of metallopeptidases and contains a double calcium site, which acts as a calcium switch for activity. The pro-segment traverses the active-site cleft in the opposite direction to the substrate, which precludes its cleavage. It is anchored to the mature enzyme through residue Arg21, which intrudes into the specificity pocket in cleft sub-site S1'. Moreover, residue Cys23 within a conserved cysteine–glycine motif blocks the catalytic zinc ion by a cysteine-switch mechanism, first described for mammalian matrix metallopeptidases. In addition, a 1.5 Å structure was obtained for a complex of mature mirolysin and a tetradecapeptide, which filled the cleft from sub-site S1' to S6'. A citrate molecule in S1 completed a product-complex mimic that unveiled the mechanism of substrate binding and cleavage by mirolysin, the catalytic domain of which was already preformed in the zymogen. These results, including a preference for cleavage before basic residues, are likely to be valid for other unicellular pappalysins derived from archaea, bacteria, cyanobacteria, algae and fungi, including archetypal ulilysin from Methanosarcina acetivorans. They may further apply, at least in part, to the multi-domain orthologues of higher organisms.

The first ab initio aspherical structure refinement against experimental X-ray structure factors for polypeptides and proteins using a fragmentation approach to break up the protein into residues and solvent, thereby speeding up quantum-crystallographic Hirshfeld atom refinement (HAR) calculations, is described. It it found that the geometric and atomic displacement parameters from the new fragHAR method are essentially unchanged from a HAR on the complete unfragmented system when tested on dipeptides, tripeptides and hexapeptides. The largest changes are for the parameters describing H atoms involved in hydrogen-bond interactions, but it is shown that these discrepancies can be removed by including the interacting fragments as a single larger fragment in the fragmentation scheme. Significant speed-ups are observed for the larger systems. Using this approach, it is possible to perform a highly parallelized HAR in reasonable times for large systems. The method has been implemented in the TONTO software.

Transforming growth factor β-1 (TGFβ-1) is a secreted signalling protein that directs many cellular processes and is an attractive target for the treatment of several diseases. The primary endogenous activity regulatory mechanism for TGFβ-1 is sequestration by its pro-peptide, latency-associated peptide (LAP), which sterically prohibits receptor binding by caging TGFβ-1. As such, recombinant LAP is promising as a protein-based therapeutic for modulating TGFβ-1 activity; however, the mechanism of binding is incompletely understood. Comparison of the crystal structure of unbound LAP (solved here to 3.5 Å resolution) with that of the bound complex shows that LAP is in a more open and extended conformation when unbound to TGFβ-1. Analysis suggests a mechanism of binding TGFβ-1 through a large-scale conformational change that includes contraction of the inter-monomer interface and caging by the `straight-jacket' domain that may occur in partnership through a loop-to-helix transition in the core jelly-roll fold. This conformational change does not appear to include a repositioning of the integrin-binding motif as previously proposed. X-ray scattering-based modelling supports this mechanism and reveals possible orientations and ensembles in solution. Although native LAP is heavily glycosylated, solution scattering experiments show that the overall folding and flexibility of unbound LAP are not influenced by glycan modification. The combination of crystallography, solution scattering and biochemical experiments reported here provide insight into the mechanism of LAP sequestration of TGFβ-1 that is of fundamental importance for therapeutic development.

This copepod Aleutha potter,officially named and described in 2007, is found in Potter Cove, King George Island, Antarctica. Copepod (Kope = Greek for “oar” Podos = […]

The post World of Copepods appeared first on Smithsonian Insider.

Rwanda’s Human Resources for Health (HRH) Program – funded in part by the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR) from 2012 to 2017 – more than tripled the country’s physician specialist workforce and produced major increases in the numbers and qualifications of nurses and midwives, says a new report from the National Academies of Sciences, Engineering, and Medicine.

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The Indian long pepper's use in traditional medicine dates back thousands of years.

This year's ALS Challenge turns away from ice buckets and and bites into the fiery goodness of a hot pepper for a great cause: amyotrophic lateral sclerosis.

Dublin Dr Pepper, the world's oldest Dr Pepper bottler, faces a lawsuit from Dr Pepper Snapple Group.

The nip in the air says it's time to transition from summer cooking to fall cooking with this end-of-summer vegetable soup.

The FDA has now confirmed that the disgusting sludge a man poured from a freshly opened Pepsi can was a dead frog or toad.

When the garden and farmers market are bursting with green bell peppers, you'll need these recipes to use them all up.

In 'agrivoltaics,' crops and solar panels not only share land and sunlight, but also help each other function more efficiently.

Peppybox, a legally-operating online marketplace for cannabis delivery has recently announced that celebrity angel investors have shown interest to fund its business and to champion it using their own personal branding.

When it comes to combating the appearance of aging skin there is nothing more successful than peptides. In the world of anti-aging, trifluoroacetyl tripeptide 2, Progeline is one of the most potent defenders against the visible signs of aging skin.

How PepsiCo is harnessing the power of design.

The chili pepper is the pride of New Mexico, but they have a problem with their beloved crop. There just aren’t enough workers to pick the peppers. Picking chili peppers can be especially grueling work even compared to other crops. So most workers are skipping chili harvests in favor of other sources of income.  As a result, small family farms have been planting less and less chili every year in favor of other less-labor intensive crops. So, scientists are trying to find ways to automate the harvest, but picking chilis turned out to be a tough job for a robot.

How To Pick A Pepper

Rose Eveleth’s podcast is called Flash Forward. Subscribe on Apple Podcasts or RadioPublic.

A method of labeling a sulfenic acid (—SOH) group of a cysteine residue in a protein; or peptide, comprises contacting said protein or peptide with a beta-ketoester to covalently couple said beta-ketoester to said cysteine residue and form a beta-ketoester-labeled cysteine residue in said protein or peptide.

The present invention generally relates to processes and methods of peptide and protein synthesis. The present invention also relates to specific compounds for use in such processes and methods. It is shown herein that peptides with a C-terminal tertiary N,N-bis(2-mercaptoethyl)-amide (BMEA) undergo N-to-S acyl transfer at weakly acidic pH to form a transient thioester which can be captured for direct ligation with a cysteinyl peptide. These C-terminal BMEA peptides are easily prepared with standard Fmoc solid-phase synthesis protocols, thus giving a very convenient access to the thioester components for native chemical ligation.

A polymeric dendrimer-like structure with four branches of monomethoxy-polyethylene glycol that can be represented as: The carboxylic group of the previous structure can be functionalized for the production of conjugates of pharmaceutical interest. The binding of this dendrimer-like polyethylene glycol to therapeutic proteins improves their in vitro and in vivo stability.

The invention relates to a polypeptide having a mutation at one or more position corresponding to T219 of SEQ ID NO: 55, wherein the polypeptide has at least 50% sequence identity with SEQ ID NO: 55, and wherein the polypeptide has permease activity.

Cyclic CRF antagonist peptides having improved properties of “drugability”. The peptides are 33 residues in length with a lactam bond between the residues in position 22 and 25; however, they may be N-terminally shortened by up to 3 residues.

To provide a diagnostic and therapeutic medicament, a bombesin analog peptide antagonist conjugate is provided which has general Formula (I), wherein A is a metal chelator comprising at least one radionuclide metal, B is a spacer linked to N-terminal of C or a covalent bond and C is a bombesin analog peptide antagonist having a sequence as claimed, where further x is an integer from 1 to 3 and n is an integer from 1 to 6. [A-(B)n]x—C (I)

A method of producing a molecularly-imprinted material comprises synthesizing a peptide, oligosaccharide or oligonucleotide on a disposable surface modified support to produce a support surface-attached peptide, oligosaccharide or oligonucleotide, providing a selected monomer mixture, contacting the monomer mixture with the support surface-attached peptide, oligosaccharide or oligonucleotide, initiating polymerisation or at least one crosslinking reaction, dissolving or degrading the support surface-attached peptide, oligosaccharide or oligonucleotide and support, and obtaining molecularly imprinted material.