Tag Archives: 龙凤419

a month ago​Man City midfielder Silva writes to FA over Mendy tweet

first_imgTagsPremiership NewsAbout the authorIan FerrisShare the loveHave your say ​Man City midfielder Silva writes to FA over Mendy tweetby Ian Ferrisa month agoSend to a friendShare the loveManchester City midfielder Bernardo Silva has written to the FA to say he regrets the fact his social media post may have unintentionally caused offence, reports BBC Sport.BBC Sport understands Bernardo personally wrote the letter, which was submitted before Thursday’s 17:00 BST deadline.Team-mate Benjamin Mendy has also written to the FA in support of Bernardo, saying he did not take offence at the posts.Bernardo is adamant he never intended to offend and his posts were not racially motivated. last_img

15 days agoWenger: Hazard can’t replace Ronaldo at Real Madrid

first_imgAbout the authorCarlos VolcanoShare the loveHave your say Wenger: Hazard can’t replace Ronaldo at Real Madridby Carlos Volcano15 days agoSend to a friendShare the loveFormer Arsenal boss Arsene Wenger doesn’t believe Eden Hazard can replace Cristiano Ronaldo at Real Madrid.The Belgian is beginning to demonstrate his qualities with Los Blancos after a tough period following his move from Chelsea.”He will be the answer but not in replacing Ronaldo that is for sure,” Wenger told beIN Sports about Hazard.”He will not score 50 goals a year because that’s now how they play football.”They need another goal scorer in Real Madrid because Benzema is now 32 and if they had someone younger around him to score the goals, maybe they could do very well.”Eden Hazard is an exceptional player to create chances to sometimes finish when he needs to do in big games.”He’s not scared of anybody – I don’t think Real have yet to see the real Hazard, he’s not as sharp physically as he can be.”That’s why I believe they will discover the real Hazard.” last_img read more

Video: Oregon State Player Intentionally Trips Referee, Gets Ejected

first_imgJarmal Reid tripped a ref during Oregon State game.jarmal reid trips refereeWe’ve all been there. In the heat of the moment, after you think you’ve been fouled on the basketball court, you look to the referee to plead your case. Oregon State’s Jarmal Reid went one step further – however. He’s in trouble for it today.Reid, during Oregon State’s contest against Utah Sunday night, was unhappy after being bumped following a steal. After falling down and seeing that no foul had been called, he intentionally stuck his foot out to trip the referee. He was promptly ejected.Jarmal Reid of Oregon State was ejected for tripping an official. Never seen this before. https://t.co/y24JrRH7Ex— Rob Dauster (@RobDauster) January 18, 2016Utah went on to win the game. Reid’s decision is now being reviewed by the Pac-12. Don’t be surprised if he doesn’t see the court for quite some time.last_img read more

ITA/TAJ Provide Easier Way For Motorists to Pay Motor Vehicle Fitness Fee

first_img Tax Administration Jamaica (TAJ) and The Island Traffic Authority (ITA) have teamed up to provide motorists with an easier way of paying their Motor Vehicle Fitness Fees. These fees can now be paid on line at www.jamaicatax.gov.jm and motorists will no longer have to visit a Tax Office to do so. Story Highlights The online payment service is expected to be rolled out in Port Antonio, Port Maria, Falmouth, Lucea and Black River Depots by the end of the calendar year. The Savanna-la-mar depot which is currently under construction will come on stream upon completion. More Information can be had by calling 1-888-Tax Help (1-888-829-4357) toll free or visit the Pay Motor Vehicle Fees hub on the TAJ website www.jamaica tax.gov.jm. Tax Administration Jamaica (TAJ) and The Island Traffic Authority (ITA) have teamed up to provide motorists with an easier way of paying their Motor Vehicle Fitness Fees. These fees can now be paid on line at www.jamaicatax.gov.jm and motorists will no longer have to visit a Tax Office to do so.The ITA Depots that will facilitate the processing of Fitness Certificates paid for on line are:SwallowfieldHarbour View and Spanish Town Road in KingstonThomasSpanish Town in St.CatherineMandeville in ManchesterAnn’s Bay in St Ann and Montego Bay, St. James.The online payment service is expected to be rolled out in Port Antonio, Port Maria, Falmouth, Lucea and Black River Depots by the end of the calendar year. The Savanna-la-mar depot which is currently under construction will come on stream upon completion.Transport and Mining Minister, Lester ‘Mike’ Henry, says the new service provision on line is in keeping with his Ministry’s thrust to make it easier for motorists to do business with government, reduce waiting time at tax offices, as well as, reducing if not eliminating opportunities for corruption. According to Minister Henry, the use of technology in the provision of services, is not only convenient, but is secure and less time consuming, as in many instances the importance of ‘TIME’ has been removed from the lives of many Jamaicans in their daily activities. The Island Traffic Authority has been implementing a New Electronic System on a phased basis since the start of the year.Meanwhile, Chief Corporate Communications Officer, at the TAJ, Meris Haughton, says the process is simple and requires motorists to log into the TAJ Payment Portal using their client login or creating an account (where applicable).According to Ms. Haughton, the customer may click on the ‘Pay Your Motor Vehicle Fees’ tab or select ‘The Motor Vehicle Fees’ option under ‘Pay Other Taxes and Fees’ and choose the option for their vehicle type. A TRN, a branch number where applicable and a valid credit are required to complete the transaction.The motorist may then print the Statement of Payment or record the Reference Number before proceeding to any of the participating ITA Depots to have the vehicle inspected and certified. Upon arrival at the ITA Depot motorists may then present The Statement of Payment or Reference Number, TRN and the date the fee was purchased.Ms. Haughton is also encouraging motorists to use the new online facility, because the onsite payment facility at the Swallowfield Depot will be eventually phased out.More Information can be had by calling 1-888-Tax Help (1-888-829-4357) toll free or visit the Pay Motor Vehicle Fees hub on the TAJ websitewww.jamaica tax.gov.jm.last_img read more

Shoreline from Breezy Castle to Harbour View to Be Restored

first_img Meanwhile, Senator Williams said that a procurement process for seats, carpets and sound equipment has been initiated for the 106-year-old Ward Theatre in Kingston. Senator Williams informed that it is noticeable that the roadway is being eroded and a meeting will be held with JSIF “for them to bring us up to date with the arrangements being put in place towards protecting the shoreline”. Story Highlights Mayor of Kingston, Senator Councillor Delroy Williams, says the Jamaica Social Investment Fund (JSIF) will be leading the restoration and protection of the shoreline from Breezy Castle (Kingston Harbour) to Harbour View. Mayor of Kingston, Senator Councillor Delroy Williams, says the Jamaica Social Investment Fund (JSIF) will be leading the restoration and protection of the shoreline from Breezy Castle (Kingston Harbour) to Harbour View.Senator Williams informed that it is noticeable that the roadway is being eroded and a meeting will be held with JSIF “for them to bring us up to date with the arrangements being put in place towards protecting the shoreline”.The Mayor was addressing councillors at the monthly sitting of the Kingston and St. Andrew Municipal Corporation at its Church Street offices in downtown Kingston, on February 13.Meanwhile, Senator Williams said that a procurement process for seats, carpets and sound equipment has been initiated for the 106-year-old Ward Theatre in Kingston.“This was uploaded to the Office of the Contractor General’s website, as is required by law,” he informed.The Mayor noted that the Tourism Ministry has committed $10 million towards the theatre’s restoration process and funds have also been committed by the Culture, Health, Arts, Sports and Education (CHASE) Fund for seats and sound equipment.“We progressed with the procurement because of these commitments. Over the next two to three weeks, we will concretise this. I just want to urge the procurement and leadership committee to ensure that we don’t miss a step, and follow them to the law,” he said.Turning to plans to beautify certain locations in Kingston and St. Andrew, the Mayor informed that more flags and other elements will be included to improve the aesthetics at the entrance of downtown Kingston at Breezy Castle.“We are also looking at some sections of Western St. Andrew, which would be the Waterhouse Division, along Spanish Town Road, entering into the Three Miles area, the Portia Simpson Miller Square, and to try and beautify that corridor,” he said.The Mayor emphasised the importance of transforming the city of Kingston, so that it will appear more attractive to visitors as well as to its residents.last_img read more

Hunter Maritime to Buy Five Bulkers from Oskar Wehr

first_imgzoom The Marshall Islands-based Hunter Maritime Acquisition Corp. has decided to buy five Capesize dry bulk carriers in an en bloc transaction from Germany’s Oskar Wehr. The ships will be purchased for USD 139.4 million from five Cyprus-based companies affiliated with one or more members of the Oskar Wehr group of companies.The vessels in question are MV Charlotte Selmer, MV Greta Selmer, MV Tom Selmer, MV Lene Selmer and MV Hugo Selmer, all of them built by Chinese shipbuilder New Times Shipbuilding.The five bulkers have a combined cargo-carrying capacity of approximately 876,352 deadweight tons and an average fleet age of approximately 6.2 years. Four vessels are employed on time charter, expiring in July 2017, August 2017, December 2017 and February 2018, respectively.“As part of the acquisition, the company expects to have the time charter agreements or other employment arrangements that are in place upon the consummation of the acquisition novated to the company or otherwise assumed by the company,” Hunter Maritime said.Once the acquisition is closed, Ambra Shipmanagement, a company affiliated with the Oskar Wehr Group, will continue to provide technical management services for the vessels and Bocimar International NV, an affiliate of Hunter Maritime, will provide commercial management services for the bulkers, according to Hunter Maritime.In connection with the acquisition which is subject to certain conditions, Hunter Maritime intends to offer to purchase up to 8.233,100 of its Class A common shares that were sold in the company’s initial public offering (IPO).last_img read more

Mastermind Toys expanding across Canada despite challenges of retail sector

first_imgTORONTO – Mastermind Toys is shrugging off the challenges that have beset the retail sector with plans to open more stores this year.The Canadian retailer said it’s opening its 56th store in Orleans, Ont. Tuesday and plans to have locations open later this year in Sudbury, Ont., Langford, B.C., Fredericton, and Toronto.The new stores are in addition to the seven Mastermind has already opened this year, while since 2011 the retailer has opened 50 new toy stores as it expands out of Toronto to now have stores in seven provinces.The latest expansion news comes a day after Toys “R” Us filed for bankruptcy protection in the United States, saying it intends to follow suit in Canada as online competition takes an increasing toll on in-person retailers.The toy giant said its roughly 1,600 global stores will continue to operate normally, with the vast majority profitable, but it has struggled with the burden of $5 billion in long-term debt.Brick and mortar retailers continue to face pressure from online competition and changing consumer taste, helping lead to high profile restructurings including Sears Canada’s bankruptcy protection this past June.last_img read more

RCMP looking for people involved after eyewitness reports alleged abduction

first_imgFORT ST. JOHN, B.C. – The Fort St. John RCMP are looking for information after an eyewitness broke up what appeared to be an attempt to abduct a child on Saturday.The RCMP responded to a call on May 12, after an eyewitness confronted a male who was allegedly trying to take a child from his mother.  The details are limited, but the RCMP are looking to speak with both the woman and the male involved in the incident.According to an eyewitness, a male was allegedly seen taking a 4 to 5-year-old child in the Subway parking lot at 100 street and 97 avenue between 10:30 a.m. and 11 a.m.  The child began screaming as did the mother, which alerted a nearby witness. The witness allegedly confronted the male and instructed him to put down the child. The male put down the child and left the scene heading on foot towards the North Peace Leisure Pool.  The mother and child also left on foot, heading westbound, towards 102 street.All three are described as being of South Asian or Middle Eastern descent.The alleged male suspect is described as being between 25 and 33-years-old, having a five o’clock shadow, with a thick neck and white button-up shirt with black shoes.The female is described as wearing a full purple burqa, with purple bands and between the age of 25 and 30 with a height of 5’4” and 170 pounds.  The child is described as wearing a white shirt with a blue collar and having black medium length hair.Police would like to confirm the wellbeing of the woman and child and would like to speak to anyone involved in this incident as well as anyone having information as to the identity of these persons.Please contact Cst PERDUE at 250-787-8100 with any information. If you wish to remain anonymous, you may call Crime Stoppers at 1-800-222-8477. Crime Stoppers tipsters do not have to provide their name, address or telephone number and may be eligible for a cash reward of up to $2000 for information leading to an arrest and charge.last_img read more

Zidane admits to not playing Bale for attitude problem

first_imgMadrid: With reports of Gareth Bale’s impending departure from Real Madrid continuing to gather steam, the Welshman spent ninety minutes of the last league match of the season for the Los Blancos on Sunday, a 0-2 defeat to Real Betis, on the bench. Speaking after the match, Real Madrid manager Zinedine Zidane said he would not have brought Bale on even if his team had been allowed an added substitution. “It is true, I did not [give Bale a chance to say goodbye],” Zidane was quoted as saying by ESPN. “If I had another substitute to make, I would not have done anything different,” he said. While youngsters Vinicius Junior and Brahim Diaz were picked over Bale in the starting XI on Sunday, Lucas Vazquez and Marco Asensio were brought on in the second half. Bale and Toni Kroos continued to warm the bench throughout. As the final whistle blew, Bale headed straightaway towards the tunnel, not waiting for the rest of the Real Madrid team. Also Read – We will push hard for Kabaddi”s inclusion in 2024 Olympics: RijijuZidane said: “I have to look at the day-to-day, and make decisions. And when there is something I do not like, or does not fit for me, I must do what I think best. It might be difficult for the player.” “We cannot forget all he has done here, but I must live in the present, think of the future. We will see [if Bale continues]. I don’t know what will happen, truthfully,” he added. Sunday’s defeat brought to an end an unflattering domestic campaign for Real Madrid. The Spanish giants have finished the season on 68 points, 19 points behind champions Barcelona. “We must accept when things go badly. I am responsible for this. We had 11 games, we won five, lost four, and in the end that is what it is. At a club like Madrid, motivation is difficult when there is nothing to play for. This is not the first bad year in the history of this club,” Zidane said.last_img read more

England debutant wins grandfather £17000

first_imgLewis Cook has won his grandfather £17,000 after making his debut for England at their international friendly against Italy on TuesdayThe Telegraph has reported that the grandfather, Trevor Burlingham, made a £500 bet back in 2014 that Cook would make his international debut for England before the age of 26.Back then, Cook was just 18 years-old and coming through the youth ranks at Championship side Leeds United with Burlingham making the bet at his local William Hill in Tadcaster, north Yorkshire for odds of 33/1.Jose Mourinho is sold on Lampard succeeding at Chelsea Tomás Pavel Ibarra Meda – September 14, 2019 Jose Mourinho wanted to give his two cents on Frank Lampard’s odds as the new Chelsea FC manager, he thinks he will succeed.There really…The now Bournemouth midfielder met his grandfather’s prediction by coming on as a 71st minute substitute for Manchester United’s Jesse Lingard in England’s 1-1 draw against Italy at Wembley.The bookies William Hill have now announced that it is the biggest payout they have done since awarding Peter Edwards £125,000 for his grandson Harry Wilson making his Wales debut in 2013. The winger was just 18 months old when his grandfather made the bet.Another famous story was when the father of former Liverpool goalkeeper Chris Kirkland won £10,000 for making his international debut with the bet having been made while the goalkeeper was 12 years-old.last_img read more

Lovren says Salah could top Messi and Ronaldo

first_imgLiverpool defender Dejan Lovren believes if Mohamed Salah leads the club to win the Champions League, he could possibly be deemed a player of the rank of Messi and Ronaldo, and even better – the best player in the world.The Reds will be facing Real Madrid in Kiev on Saturday night as they will be looking to add a sixth European Cup to their collection. Los Blancos, on the other side, will be trying to get their hands on their third consecutive Champions League title and fourth in the last five years.Ahead of the clash, Lovren voiced his opinion that Salah could easily compete with and even win over Messi and Ronaldo for the Ballon d’Or.“I spoke to Mo about that. It is still quite an early stage but if we win definitely he is one of the contenders,” said Lovren, according to Sport360.divock origi, liverpoolReport: Origi cause Klopp injury concerns George Patchias – September 14, 2019 Divock Origi injury in today’s game against Newcastle is a cause for concern for Jurgen Klopp.Perhaps with one eye on Tuesday’s trip to Italy…“When you score 44 in all, definitely. When you look, Messi, Ronaldo, Mo Salah, he deserves to be in the top three.”“He has the quality, the world-class experience already.”“He is so calm, a man down to earth and he deserves every credit for every goal he scored for now and definitely we will help him achieve this dream,” Lovren shared.last_img read more

Sweden – England lineups announced

first_imgThe lineups for the Sweden – England World Cup 2018 quarter-final fixture have been announced.There are no surprises on either side. Both coaches are going with tested lineups and tactics.Sweden starting lineup vs. EnglandGoalkeeper – Robin Olsen Defenders – Ludwig Augustinsson, Andreas Granqvist, Victor Lindelof and Emil Krafth Midfielders – Sebastian Larsson, Viktor Claesson, Albin Ekdal and Emil Forsberg Forwards – Ola Toivonen and Marcus BergJanne Andersson is without his starting right back Mikael Lustig, who is suspended. Emil Krafth takes his spot. Viktor Claesson and Albin Ekdal are in danger of missing a potential semi-final in case of another booking today.England starting lineup vs. SwedenGoalkeeper – Jordan Pickford Defenders – Kieran Trippier, Kyle Walker, John Stones, Harry Maguire and Ashley Young Midfielders – Jordan Henderson, Dele Alli, Jesse Lingard and Raheem Sterling Forward – Harry KaneGareth Southgate’s starting lineup is exactly the same one which started the game against Colombia. Kyle Walker, Ruben Loftus-Cheek, Jordan Henderson and Jesse Lingard go into the game on one booking and will be suspended for the semi-final if they are to receive yellow cards today.last_img read more

For Rafa Mir his spell with Wolves was difficult

first_imgThe 21-year-old forward is currently very happy to be back in the Spanish La Liga, playing with Las Palmas on loanSpanish forward Rafa Mir started his professional career with Valencia B in 2015, and the same year he played for the first team in the Spanish La Liga.But after only two matches in the first division, he didn’t see any more action and was sold in 2018 to the Wolverhampton Wanderers in the English Premier League.And history repeated itself.Two matches with the Wolves made him very frustrated, so he was loaned to Las Palmas in the Spanish La Liga.“It was a very hard time for me and my family, what hurt the most was not having the minutes I wanted,” he was quoted by the Birmingham Mail.Premier LeaguePremier League Betting: Match-day 5 Stuart Heath – September 14, 2019 Going into the Premier League’s match-day five with a gap already beginning to form at the top of the league. We will take a…“If I had had the time I would have adapted better, it was a period of adaptation and it is not easy to enter mid-year.”“In the end, it was the decision that was made and I am happy on the one hand,” he added.“When a big club looks at you, every player thinks of moving to that side.”“It is true that depends on others because there are advisors or sports directors,” he commented.“It could not be and I am left with the positive that I got from England, we have to keep working and why not go [to Real Madrid] someday?”last_img read more

Changes Made To Workplace Smoking Ban Bill

first_imgFacebook0TwitterEmailPrintFriendly分享Senate Bill 63, the Smokefree Workplace bill, advanced out of the House Rules Committee last night, with a few adjustments. The House Rules Committee advanced a rewrite of the smoke-free workplace bill that would allow communities to opt out via local elections and excludes e-cigarettes and marijuana from the definition of smoking. The original bill had widespread support, but House Rules Committee Chair Gabrielle LeDoux refused to schedule it for a vote on the House floor. She said the state should not force municipalities into a program they may not want. Senator Peter Micciche (R-K-Pen) is the sponsor of the bill that was introduced in 2016 that ultimately failed after clearing the Senate. If the bill passes the House, the Senate must decide whether to accept the new changes.last_img read more

FEMARequired Insulation Might Not Be Great For Houstons Climate

first_img Share “dunktanktechnician” via FlickrSpray foam insulation being installed in Houston.A FEMA-required building material that’s supposed to protect buildings from flooding could cause problems in some Houston homes.The agency says in flood-prone areas, spray-foam insulation or “closed-cell” plastic foam has to be used in floors, walls or ceilings during repairs or for new buildings covered by the National Flood Insurance Program. According to FEMA, the material is “highly resistant” to flood damage, and can be cleaned after a flood to remove most pollutants.But some say those materials are bad for humid climates.“Foam in Houston is a horrible thing,” said Tom Tynan, Director of the Construction Trades Department at Houston Community College and host of a local home repair radio show.“It doesn’t breathe, and so what you’re doing is creating a terrarium in a wall,” he said. “It’ll create its own little micro-climate.”The Houston remodeling company Creative Property Restoration, Inc. said that “closed cell” spray foam insulation can trap moisture inside walls, which could lead to mold, but that other types of foam called “open cell” wouldn’t trap moisture.Still, companies that sell this type of insulation use the FEMA requirement to promote their products online, and not complying with the rules could lead to more expensive flood insurance.FEMA did not make anyone available for an interview about why it requires this particular kind of insulation in flood-prone areas.last_img read more

Targeted drug therapy with carrier links to tertiary and heteroaryl amines

first_imgQuaternary-ammonium-salt linkers can be proteolytically or reductively cleaved on cell entry and tracelessly release tertiary and heteroaryl amines. Credit: (c) Nature Chemistry (2016) doi:10.1038/nchem.2635 (Phys.org)—Beyond designing a drug that will attack cancer cells or bacterial cells, drug design also involves figuring out how the drug can safely enter the body and find its target before doing its work. However, many drugs never make it to their desired target either because of solubility issues or inability to access certain parts of the cell. That is where carriers come in. Carriers are like molecular taxis that latch onto a small-molecule drug and transport it to its target location. Journal information: Nature Chemistry Citation: Targeted drug therapy with carrier links to tertiary and heteroaryl amines (2016, November 3) retrieved 18 August 2019 from https://phys.org/news/2016-11-drug-therapy-carrier-links-tertiary.html These molecular taxis need to connect to the drug in such a way that they safely take it to the location, but the connection must also be reversible so the carrier can eventually release the drug. There are very few types of chemical bonds that can do this and the ones that can are limited in scope.A group of scientists from Genentech, Inc. have devised a synthetic scheme that is generalizable, protecting-group free, and allows for a carrier linker to attach to tertiary or heteroaryl amines via a quaternary ammonium salt. Additionally, because it is a charged species, it is more water soluble than typical carrier molecules and, therefore, may alleviate the problems associated with aggregation. These linkers can be set up to be cleaved either by proteases in the lysosome or reducing agents in the cytosol. This work appears in Nature Chemistry.”Enabling the reversible connection of tertiary and heteroaryl amines allows us to consider many new drugs, previously unamenable for targeted therapy,” Dr. Thomas Pillow told Phys.org.The ability to attach a linker to a tertiary amine or a heteroaryl amine is of interest because there are several known anticancer and antibacterial drugs that that have these functional groups. These groups often cannot be converted to a secondary or primary amine because of synthetic complexities or diminished drug potency. These drugs require a carrier molecule in order to be most effective in the body, but most carrier molecules previously could only be connected to primary or secondary amines.Additionally, many anticancer and antibacterial drugs are hydrophobic. But, the body is a predominantly aqueous environment. This means that, upon entering the body, the hydrophobic molecules tend to aggregate, which can cause problems with bodily systems or protein uptake. Notably, when the Genentech scientists attached a tertiary amine to a linker via a quaternary ammonium salt, it became more hydrophilic suggesting that this might be a good option for countering the aggregation problem. The first step was to determine if a tertiary amine could be reversibly attached to a chemical linker. To test their proposed linker connection, a p-aminobenzyl quarternary ammonium salt, they chose a known dipeptide-cleavable trigger: valine-citrulline (ValCit) which cleaves in the presence of cathepsin B. Incubation of their linker in buffer demonstrated that the quaternary ammonium salts were stable, and exposure to cathepsin B resulted in cleavage at the aniline amide and generation of the tertiary amine as expected. Carbon-carbon bond formation at selective aliphatic carbon sites More information: Leanna R. Staben et al. Targeted drug delivery through the traceless release of tertiary and heteroaryl amines from antibody–drug conjugates, Nature Chemistry (2016). DOI: 10.1038/nchem.2635AbstractThe reversible attachment of a small-molecule drug to a carrier for targeted delivery can improve pharmacokinetics and the therapeutic index. Previous studies have reported the delivery of molecules that contain primary and secondary amines via an amide or carbamate bond; however, the ability to employ tertiary-amine-containing bioactive molecules has been elusive. Here we describe a bioreversible linkage based on a quaternary ammonium that can be used to connect a broad array of tertiary and heteroaryl amines to a carrier protein. Using a concise, protecting-group-free synthesis we demonstrate the chemoselective modification of 12 complex molecules that contain a range of reactive functional groups. We also show the utility of this connection with both protease-cleavable and reductively cleavable antibody–drug conjugates that were effective and stable in vitro and in vivo. Studies with a tertiary-amine-containing antibiotic show that the resulting antibody–antibiotic conjugate provided appropriate stability and release characteristics and led to an unexpected improvement in activity over the conjugates previously connected via a carbamate. Explore further This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only. The next step was to optimize their synthesis to make it simple and generalizable so it can be used for drug screening. In particular, the synthesis could not involve the use of protecting groups and the carrier molecule needed to preferentially react with the tertiary amine on the small molecule drug. After developing the experimental conditions for their reaction, Staben et al. then tested the stability and release of their protease-cleavable linker with a variety of molecules containing tertiary and heteroaryl amines. Good stability and drug release was demonstrated with several of these conjugates.Thus far, Staben et al. have been looking at the cleavage of peptide bonds. Disulfide bonds are another bond that can be set up as a bioactive trigger that is reduced by intracellular GSH. They tested their system by cleaving the disulfide bond and were able to generate the free tubulysin drug. In the field of targeted therapies, antibody-drug conjugates have gained ground as a way to target cancer cells or invading bacteria. Prior research by this team demonstrated that an antibody-antibiotic conjugate was able to successfully clear methicillin-resistant S. aureus (MRSA) infections. For the current research, they linked the tertiary amine of a rifamycin analog to their quaternary ammonium salt linker and found that in vitro tests showed a large reduction in the number of intracellular MRSA bacteria, a typically difficult-to-treat bacterial infection. According to Dr. Pillow, “This novel linker connection expands the universe of drugs for targeted therapy, opening up new possibilities for the treatment of cancer and infectious disease.” © 2016 Phys.orglast_img read more