Abstract

Design approaches for inhibitors of protein-protein interactions are rare, but highly sought after. Here, we report that O-phosphorylation of simple derivatives of the natural products dihydrocapsaicin and N-vanillylnonanamide leads to inhibitors of the SH2 domain of the transcription factor STAT5b. The most potent molecule is obtained from dihydrocapsaicin in only three synthetic steps. It has submicromolar affinity for the SH2 domain of STAT5b (Ki = 0.34 µM), whilst displaying 35-fold selectivity over the highly homologous STAT5a (Ki = 13.0 µM). The corresponding pivaloyloxymethyl ester inhibits STAT5b with selectivity over STAT5a in human tumor cells. Importantly, it inhibits cell viability and induces apoptosis in human tumor cells in a STAT5-dependent manner. Our data validate O-phosphorylation of appropriately preselected natural products or natural product derivatives as a semi-rational design approach for small molecules that selectively inhibit phosphorylation-dependent protein-protein interaction domains in cultured human tumor cells.

http://pubs.acs.org/doi/pdf/10.1021/acschembio.5b00817

My work has been published in Angewandte Chemie. This molecule Stafib-1 is the first nanomolar active small molecule inhibitors of oncogenic STAT5b over its close isoform STAT5a.

http://onlinelibrary.wiley.com/doi/10.1002/anie.201410672/epdf

Recent offers for Indians

Dear Friends, 

       Go through the following scholarship links which are specifically for Indians so that there are more feasibility to afford at least one of them. Try, try  and try again until you posses it. All the very best for your all attempts. 

1. http://scholarship-positions.com/uk-scholarships-for-indian-students-by-charles-wallace-india-trust-cwit/2011/11/12/

2. http://scholarship-positions.com/scholarships-for-indian-students-chevening-rolls-royce-awards-2012/2011/11/12/

3. http://scholarship-positions.com/2012-2013-commonwealth-scholarships-for-developing-commonwealth-country-citizens-uk/2011/07/21/

4. http://scholarship-positions.com/project-fellowship-in-the-department-of-biotechnology-at-university-of-calcutta-india/2011/11/04/

5. http://scholarship-positions.com/special-scholarship-scheme-for-students-of-jammu-and-kashmir/2011/11/04/

6. http://scholarship-positions.com/2012-khorana-program-summer-in-for-us-students-in-india/2011/10/18/

I hope all these are useful. 

Best regards, 

Nagu

  

Deewali Wishes with an Interview with Dr. Wolfgang Reindl

Dear Friends, 

        We wish you all Happy and Prosperous Diwali. We wish you all as well to fill your life with full of awesome feelings of happiness. Gathering native friends, relatives and neighbors are the specialties of this festival. Hope you all enjoy it by sharing sweets and sweet feelings with this moment. 

        By the way, we come up with an interview with Dr. Wolfgang Reindl who is a scientist in Evotech, Hamburg, Germany. He has done his doctoral studies at Maxplank Institute of Biochemistry, Munich, Germany (under the supervision of Prof. Thorsten Berg). For post doctoral studies, he went to Lawrence Berkeley National  Laboratory, California, USA where he had completed his job and returned back to service his Motherland (Germany).

        As it is in the previous interview, mostly same questions have interviewed him. This is posted here for your view, 

Nag: Why did you choose Biochemistry in your carrier? 

Dr. Reindl:  Basically, I am fascinated in drug developments for current challenging diseases and malignant tumors. A friend of mine who is also interested in Biochemistry suggested me to chose the same in my carrier in order to shine in the field of drug development. 

Nag: How long your PhD was? Few words about the projects you handled.

Dr. Reindl: It was roughly 4 years including defense (viva-voice examination). I started on Oct. 2004 and ended on July 2008. The project I handled "Discovery of inhibitors of Polo-Box domain of Polo-like Kinase-1/PLK-1".  

Nag: What was the critical project you handled during the course of your PhD? Were you successful? 

Dr. Reindl: That itself was the critical project I had came across. Of course, I was successful which was proved from my published articles. 

Nag: How many publications do you have right now and how many from your PhD works? 

Dr. Reindl: I have 11 publications out of them 7 are from my PhD works. You can access them from the below links PhD publications, PDF publications.

Nag: What was the secret of your successful carrier? 

Dr. Reindl: I can say hard work with confident are most crucial for all greatest achievements. So, I am not exception to this. Moreover, there are no secrets for great accomplishment, since we have well known keys such as hard work and confident. Of course, I have worked hard and believed my work with no comparison. At least 50 to 60 hours per week I used to work. Whenever there were funny colleagues around me, hours passed like minutes with lots of crazy events. So, I never felt like I am moving with burden. Make your surrounding with lots of fun, then you will realize your refreshments.

Nag: Could you share productivity tips which you had been following?

Dr. Reindl: Of course, I can say few...

1) Plan everyday before you start your work ( at least 10 min)

2) Maintain proper and detailed lab notebook. It will be very useful than anything else. Mentioning least information will also be a good idea. You can realize it later. 

3) Electronic notebooks like OneNote (Demo video) is the best idea to increase your productivity because you do not need to write the same reactions and procedures when you want to do it again. You can just copy-paste it from the old reactions.  Additionally, you can have it whenever and wherever you want.

4) To write publication article, you can use EndNote. 

5) Maintaining the lecture notes also in electronically is a good idea when we are in need of it. When it is in paper format, we do not go through it usually. 

Nag: What is your message to both Chemists and Biochemists? 

Dr. Reindl: Broadened vision will help us for innovative ideas. Sticking on the single field will not. Combination of Chemistry and Biology is called Chemical Biology. Chemists should be knowing of at least basics of Biology and vice versa will surely step into the great inventions. Abroad experiences are considered to be very important for very one in various fields. This is because of globalization.

      Dear Friends, we hope you have got some important points from this tiny conversation. Yours comments are most welcomed. Warm Diwali wishes again. Have a nice day. 

Best regards, 

Nagu & Kalai

Happy Deewali

Dear Friends, 

       We are gald to deliver our heartiest Deewali Wishes to you all. I know this is one of the important and joyalble festivals in India. I hope everyone is enjoying it with their parents and friends with lots of crakers and sweets. Have a nice day. 

Great things happen

Nagu Kalai

Interview with Dr. Philipp Heretsch

Dear Friends, 

          We hope you all are doing well and trying to achieving as biggest as possible. Well, today We come up with an interesting event and will be much useful to you all. I have interviewed Dr. Philipp Heretsch, University of Leipzig, Germany regarding his experiences during his doctoral studies. He has got post doctoral postion in California. I am really impressed by him that is why I have interviewed him and sharing with you all. This small conversation is posted here. 

Nag:  How many year did you spend for your PhD?

Dr.Heretsch: About 3 year. I have started my PhD on March 2006 and completed it on June 2009 including public viva voice exam (defence exam). 

 

Nag: How many publication have you published till now?

Dr. Heretsch: Totally 8 publications have been published and one more is in communication with concerned publisher. They are, 

JACS (1)

ANGEW CHEMIE (INTERNATIONAL EDITION) (3)

ORGANIC LETTERS (1)

SYNTHESIS (1)

BIOORGANIC MED.CHEM (1)

I do not remember the 8th one. Few links are here,

1) http://www3.interscience.wiley.com/journal/123341155/abstract?CRETRY=1&SRETRY=0

2) http://pubs.acs.org/doi/abs/10.1021/ol902270f

3) http://www3.interscience.wiley.com/journal/117903733/abstract

4) https://www.thieme-connect.de/DOI/DOI?10.1055/s-2007-983843

Nag: What was the critical reaction you proceeded during your studies?

Dr. Heretsch: It is a tranformation of exo double bond into endo double bond. I have tried this reaction many times and spent nearly 8 weeks. Finally I achieved that molecule. That reaction can not be written here. 

Nag: Can you remember the problems you faced during PhD thesis writing?

Dr. Heretsch: I do not think that there were problems during this period since I have analysed specrta and wrote procedures during the experiments. I did not want to make me in trouble by writing everthing only at the time of thesis. I organized to finish them simultaneously during my experiments so that I combined all of the procedure and included the introduction and conclusion parts. Hence, it was very easy for me at that time. 

Nag: What did you plan to do during PhD, what you did and what you could not?Dr. Heretsch: I was given a scheme on natural product synthesis. So my entire focus was to achieve that molecule and not to plan other things. I achieved it and happy now. Hence, it is not necessary to create several plans and worring on this. Focus on one and get it. Life and chemistry are very simple to deal not for trouble. 

Nag: How many hours did you spend per week and did you work day and night continuously?

Dr. Heretsch: 60 to 70 hours are enough per week. I worked 6 and 1/2 days per week. From 8 am to 9 pm. Whatever reaction I wanted start, I did it before lunch so that we can monitor it regularly and if it is finished soon then we can do work up and purification at the same day. But if we start the reaction in the after noon session, it will not be fair enough, I think. Moreover, lab work is not only important for the researchers and also strong rudimental and advanced skills are mandatory for outstanding succeedings. 

Nag: How did you start all of your reactions whether after checking mechanism and using scifinder or just get procedure and start reaction?

Dr. Heretsch: At first I think about the reaction whether it is feasible or not. I create my own idea about it and check scifinder. Sometimes my simple ideas could have been done  by noone. In that case I try my own scheme to get succeed. Conclusively, I always check mechanism and scifinder before all of my reactions. 

Nag: The schemes on which you worked and published were prepared by you or your supervisor? 

Dr. Heretsch: The idea and retro synthetic routes were from my supervisor. But the scheme did not work in somecases then I modified it. After several modifications only I could achieve my target molecule. 

Nag: What is your future plan (Academic/Industry)?

Dr. Heretsch: I am flexible with both. I am not sure which will be my profession. After completing my post doctorate, I will be back to my mother country (Germany). Then only I can decide it. If I get a better position in an industry, I wont avoid it. 

Nag: What is your message to organic chemists now?

Dr. Heretsch: No matter about on which you are working but the thing is you must understand for what you are working. You must have clear idea about your work. The important of all of your reactions must been known. Moreover, regularity will bring you very near to success. All the best. Have a nice day and research. Byeeeeeeeeeee. 

          Dear friends, we hope that this will be more helpful for you to consider your new ideas and make some decisions during research. He is really a great achiever, try to follow some of his suggestions and get succeed. Have fun and try for best. 

Best regards, 

Nagarajan & Kalaiselvi

 

Dear Friends,

          Here you can find two open positions in Chemistry. Have a fun and good luck

http://www8.umu.se/umu/aktuellt/arkiv/lediga_tjanster/313-510-10.html

http://www.scholarships-links.com/viewdetail/1329/Ph.D.-position-in-Natural-Science-specialising-Chemistry.html

Best regards,

Nagarajan E

New Info

Dear Friends, 

          I am really glad to write today's blog with some new offers and information. I did not find any new offers last weeks, hence I could not update the blog. 

          We often use google search engine in order to find PhD offfers. If we can find a specific site for this purpose, it will be much useful for the searchers, am I right? Yes, you can go and search worldwide offers in varieties of field here, 

          http://college-university-links.com/

          Additionally, for the candidates who want to develop and modify their covering letter, those go and see the following sites

1. Harvard University – Cover Letters and Other Job Search Correspondencehttp://www.ocs.fas.harvard.edu/students/gsas/cvs_and_cover_letters.pdf

2.  Massachusetts Institute of Technology- Smart Cover Letters 
http://web.mit.edu/career/www/guide/coverletters.pdf

3.  California State University, USA, Cover Letter Exampleshttp://www.csuchico.edu/plc/coverltr-ex.html

4.  Rensselaer Polytechnic Institute Sample Cover Letters
http://www.rpi.edu/web/writingcenter/cover_letter.html

5.  Morningside College Sample Cover Letters
http://www.morningside.edu/student_life/careers/sampleletter.cfm

6.  Ball State University Cover Letter Guide
http://www.bsu.edu/students/careers/documents/coverltr/

7.  Vanderbilt University Career Center Cover letters

http://www.vanderbilt.edu/career/students/coverLetterSamples.php?search=sample%20cover%20letter

8.  Basic Sample Cover Letters,The University of Texas at Arlington
http://www.uta.edu/engineering/coopeng/cover-sample.pdf (PDF)

9.  IPFW: Career Services: Students: Sample Cover Letters
http://www.ipfw.edu/career/students/exploring/coverletter.shtml

10.   Writing Professional Cover Letters, Career Services at the University of Wisconsin – Green Bay
http://www.uwgb.edu/careers/Professional_Letters_Samples.htm

         Furthermore, you can find several PhD positions in Europe, mostly in Netherlands, 

•      

• http://www.scholarships-links.com/viewbyfield/field/Chemistry/Chemistry-Scholarships/

For more information, you can visit: http://www.scholarships-links.com/

       I hope the above information will be useful for you. Have a  nice day. 

Best regards, 

Nagarajan E

New offers

Dear Friends,

      Here are few positions in Denmark:

* http://www.farma.ku.dk/index.php?id=3650 which covers totally 5 positions in various fields of Chemistry

* http://www.farma.ku.dk/index.php?id=8206 which is more helpful for the candidates who are interested in both biochemistry and biology.

  I hope this will be fruitful for you all, since these two sites include many positions in Denmark. All the best for your all attempts.

  Have a nice day.

Best regards, Publish Post

Nagu and Kalai

New offers and this week's quote

Dear Friends,

         We wish you all happy Ester day. This week I come up with few new and interesting positions in Chemistry.

* http://www.scholarships-links.com/viewdetail/1310/PhD-student-(2x2-jaar)-photovoltaic-solar-energy-conversion.html?utm_source=feedburner&utm_medium=email&utm_campaign=Feed:+Scholarships-links+(Scholarships-Links.com)

* http://www.scholarships-links.com/viewdetail/1309/Admission-in-funded-Phd-program-at-NRW-Graduate-School-of-Chemistry.html?utm_source=feedburner&utm_medium=email&utm_campaign=Feed:+Scholarships-links+(Scholarships-Links.com)

      I would like to inform you all that Erasmus Mundus is one of the best fellowships in Europe for both masters and doctoral studies. Initially It was only for masters but for last few years Erasmus is offered for PhD programs too. So that I suggest you people to go and visit the available fellowships for your corresponding field of interest. The below link will give the information about the Erasmus PhD programs.

* http://www.eur.nl/english/prospective/phd/

* http://www.bmg.eur.nl/hepl/ (this is for masters and PhD)

     The following link will give guide you to pursue masters in pharmaceutical sciences

* http://www.farma.ku.dk/index.php?id=4651

     This week's new quote is from Albert. Einstein, it is considered that an extraordinary sentence in the world which illustrates that Visualization leads to success or target or what we want to be. We must be in dream of what we want or want to be. Say an example, if we want to afford Noble prize, he suggests that we have feel that we got Noble prize, have to think that we are giving Noble lecture in front of all the esteemed scientists in the world at Sweden Noble auditorium. Then we can achieve what we want. So Feel your target and reach it soon.

Have a nice day.

Till next week,

Nagarajan & Kalaiselvi