The Date
U.S. Department of Homeland Security
Bureau of Citizenship and Immigration Services
To Whom It May Concern:
I am delighted to write this letter of evaluation on behalf of Dr. Li documenting his research contributions.
Currently I am the ABC Professor of Chemistry in the XXX Research Institute. I was elected as a member of the American Academy of Arts and Sciences (19XX) and the US National Academy of Sciences (199X). In addition I am the recipient of the Searle Scholar Award in Biomedical Sciences (19XX), the Presidential Young Investigator Award in Chemistry (19XX), the American Chemical Society A.C. Cope Scholar Award (19XX), the American Chemical Society XXX Award in Chemistry (19XX), and the Presidential XXX Award (200X). I serve as Editor-in-Chief of XXX and as an executive board member of the XXX Publications. I was a board member of the U.S. National Research Council on Chemical Sciences and Technology (19XX–200X). I am currently a scientific advisor of the XXX Institute and a founding scientist of XXX Pharmaceuticals, Inc.
My research interests are in the broad areas of organic chemistry, including but not limited to: development of new reactions, study of XXX-mediated biological recognition, design and synthesis of mechanism-based inhibitors of enzymes, development microarrays for high-throughput screening and study of reaction mechanisms. I am the author and co-author of over 470 publications, 60 patents and four books (book titles). So far I have trained ## Ph.D. graduate students and over ### postdoctoral researchers.
Dr. Li came to my group from Professor Bush’s group where he did an outstanding job of applying organic chemistry to probe the molecular basis of enzymatic reactions. In my opinion his most significant contribution to organic chemistry is the development of ABC protecting group as a highly effective mask for XYZ functionality in carbohydrate derivatives. When a chemical reaction is to be carried out selectively at one reactive site of a multifunctional starting material, other reactive sites must be temporarily blocked (or protected). A carbohydrate molecule presents a challenge for protecting groups since it has a lot of seemingly identical hydroxyl groups, whose selective protection is highly desired. The ABC protecting group answers the challenge almost perfectly. It reacts selectively with XYZ in good yield to give a protected molecule. The rigidity resulting from the ABC group not only confers stability on the protected molecule during many standard synthetic manipulations common to organic synthesis, but also provides an element for conformational control that can be exploited in subsequent reactions. Finally when time has come, it can be readily removed with simple DEF reagents to reveal the original XYZ functionality.
In fact Dr. Li was the first person in the world to demonstrate the synthetic utility of the ABC group. He used this methodology to construct several novel inhibitors for enzyme 1 and publish his results in 199X. Since then John Doe of GHI University, who is an established authority in organic chemistry, has conducted systematic studies of ABC protecting group and declared its superiority for XYZ protection in organic synthesis in a review article (Chem. Rev. 200X, XXX, XX-XX). Due to its significance to organic synthesis the ABC protecting group was highlighted in a book Protective Groups in Organic Chemistry (Greene, T.W.; Wuts, P.G.M. 3rd ed.; Wiley: New York, 1999, p. XXX), a reference book of “must read” in the field of organic chemistry. This is another testimony that Dr. Li’s discovery of ABC protecting group has been recognized internationally.
I have a long history of interest in and devotion to XXX chemistry and its application to drug discovery. Despite the important roles that XXXX play in numerous biological recognition events (e.g., bacterial and viral infection, immune response, cancer metastasis, and inflammatory reactions) the molecular details of these recognition processes are generally not well understood, and consequently the pace of development of XXX-based therapeutics has been relatively slow. Of particular interest to our group is the enzyme 2, which play a fundamental role in the biosynthesis of many important biological molecules involved in inflammation and tumor metastasis.
As a postdoctoral researcher in my group, Dr. Li played a key role in our attempt to synthesize and evaluate transition-state analog inhibitors of enzyme 2. This program was supported by the Nation Institute of Health and the XXX Institute. For the last fifty years, there has been a strong belief in the scientific community that an enzyme has the ability to lower the energy of the transition-state for the reaction it catalyzed. Stable compounds that resembled the transition-state (transition-state analogs) have proven to be competitive inhibitors of the corresponding enzyme. Following this principle Dr. Li proposed and developed analogs of OPQ, which resemble the geometry of the OPQ moiety in the transition-state of enzyme 2. Specifically he designed a cyclic ring to mimic the flattened conformation of the OPQ moiety, which was an innovative idea. This new ring is chemically more stable than OPQ and might provide stability in vivo as well. When linked to CDF, a nucleotide that provides extra binding to enzyme 2, the newly generated transition-state analog was indeed a potent inhibitor of enzyme 2.
Dr. Li’s work provided evidence that the conformation of the OPQ ring is important to the transition-state of enzyme 2 in addition to the charge on OPQ ring. Furthermore, it suggested that the majority of the binding energy of enzyme 2 for its substrates lies at the nucleotide CDF moiety. This is very important since the enzymatic reaction of enzyme 2 involves a complex four-partner transition-state. By focusing on the factors critical to enzyme binding we can develop potent inhibitors rationally and more efficiently. His work was published in Angew. Chem. Int. Ed., which is a peer-reviewed and internationally circulated journal. This publication was yet another indication that underlines the enormous contributions Dr. Li and his cutting-edge research have brought to the advancement of the scientific community and human health. It should be noted that inhibitors of enzyme 2 may have potential medicinal applications as anti-inflammatory or anti-tumor agents.
Overall Dr. Li’s broad experiences in chemistry and comprehensive experimental skills have established himself as an outstanding scientist. I hope that Dr. Li remains on a permanent basis in the United States where his continued research in organic and medicinal chemistry will provide more contributions and prosperity to our beloved nation.
Sincerely,
Name and Title
U.S. Department of Homeland Security
Bureau of Citizenship and Immigration Services
To Whom It May Concern:
I am delighted to write this letter of evaluation on behalf of Dr. Li documenting his research contributions.
Currently I am the ABC Professor of Chemistry in the XXX Research Institute. I was elected as a member of the American Academy of Arts and Sciences (19XX) and the US National Academy of Sciences (199X). In addition I am the recipient of the Searle Scholar Award in Biomedical Sciences (19XX), the Presidential Young Investigator Award in Chemistry (19XX), the American Chemical Society A.C. Cope Scholar Award (19XX), the American Chemical Society XXX Award in Chemistry (19XX), and the Presidential XXX Award (200X). I serve as Editor-in-Chief of XXX and as an executive board member of the XXX Publications. I was a board member of the U.S. National Research Council on Chemical Sciences and Technology (19XX–200X). I am currently a scientific advisor of the XXX Institute and a founding scientist of XXX Pharmaceuticals, Inc.
My research interests are in the broad areas of organic chemistry, including but not limited to: development of new reactions, study of XXX-mediated biological recognition, design and synthesis of mechanism-based inhibitors of enzymes, development microarrays for high-throughput screening and study of reaction mechanisms. I am the author and co-author of over 470 publications, 60 patents and four books (book titles). So far I have trained ## Ph.D. graduate students and over ### postdoctoral researchers.
Dr. Li came to my group from Professor Bush’s group where he did an outstanding job of applying organic chemistry to probe the molecular basis of enzymatic reactions. In my opinion his most significant contribution to organic chemistry is the development of ABC protecting group as a highly effective mask for XYZ functionality in carbohydrate derivatives. When a chemical reaction is to be carried out selectively at one reactive site of a multifunctional starting material, other reactive sites must be temporarily blocked (or protected). A carbohydrate molecule presents a challenge for protecting groups since it has a lot of seemingly identical hydroxyl groups, whose selective protection is highly desired. The ABC protecting group answers the challenge almost perfectly. It reacts selectively with XYZ in good yield to give a protected molecule. The rigidity resulting from the ABC group not only confers stability on the protected molecule during many standard synthetic manipulations common to organic synthesis, but also provides an element for conformational control that can be exploited in subsequent reactions. Finally when time has come, it can be readily removed with simple DEF reagents to reveal the original XYZ functionality.
In fact Dr. Li was the first person in the world to demonstrate the synthetic utility of the ABC group. He used this methodology to construct several novel inhibitors for enzyme 1 and publish his results in 199X. Since then John Doe of GHI University, who is an established authority in organic chemistry, has conducted systematic studies of ABC protecting group and declared its superiority for XYZ protection in organic synthesis in a review article (Chem. Rev. 200X, XXX, XX-XX). Due to its significance to organic synthesis the ABC protecting group was highlighted in a book Protective Groups in Organic Chemistry (Greene, T.W.; Wuts, P.G.M. 3rd ed.; Wiley: New York, 1999, p. XXX), a reference book of “must read” in the field of organic chemistry. This is another testimony that Dr. Li’s discovery of ABC protecting group has been recognized internationally.
I have a long history of interest in and devotion to XXX chemistry and its application to drug discovery. Despite the important roles that XXXX play in numerous biological recognition events (e.g., bacterial and viral infection, immune response, cancer metastasis, and inflammatory reactions) the molecular details of these recognition processes are generally not well understood, and consequently the pace of development of XXX-based therapeutics has been relatively slow. Of particular interest to our group is the enzyme 2, which play a fundamental role in the biosynthesis of many important biological molecules involved in inflammation and tumor metastasis.
As a postdoctoral researcher in my group, Dr. Li played a key role in our attempt to synthesize and evaluate transition-state analog inhibitors of enzyme 2. This program was supported by the Nation Institute of Health and the XXX Institute. For the last fifty years, there has been a strong belief in the scientific community that an enzyme has the ability to lower the energy of the transition-state for the reaction it catalyzed. Stable compounds that resembled the transition-state (transition-state analogs) have proven to be competitive inhibitors of the corresponding enzyme. Following this principle Dr. Li proposed and developed analogs of OPQ, which resemble the geometry of the OPQ moiety in the transition-state of enzyme 2. Specifically he designed a cyclic ring to mimic the flattened conformation of the OPQ moiety, which was an innovative idea. This new ring is chemically more stable than OPQ and might provide stability in vivo as well. When linked to CDF, a nucleotide that provides extra binding to enzyme 2, the newly generated transition-state analog was indeed a potent inhibitor of enzyme 2.
Dr. Li’s work provided evidence that the conformation of the OPQ ring is important to the transition-state of enzyme 2 in addition to the charge on OPQ ring. Furthermore, it suggested that the majority of the binding energy of enzyme 2 for its substrates lies at the nucleotide CDF moiety. This is very important since the enzymatic reaction of enzyme 2 involves a complex four-partner transition-state. By focusing on the factors critical to enzyme binding we can develop potent inhibitors rationally and more efficiently. His work was published in Angew. Chem. Int. Ed., which is a peer-reviewed and internationally circulated journal. This publication was yet another indication that underlines the enormous contributions Dr. Li and his cutting-edge research have brought to the advancement of the scientific community and human health. It should be noted that inhibitors of enzyme 2 may have potential medicinal applications as anti-inflammatory or anti-tumor agents.
Overall Dr. Li’s broad experiences in chemistry and comprehensive experimental skills have established himself as an outstanding scientist. I hope that Dr. Li remains on a permanent basis in the United States where his continued research in organic and medicinal chemistry will provide more contributions and prosperity to our beloved nation.
Sincerely,
Name and Title
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