Our research lies at the interface of organic synthesis, bio-organic chemistry and molecular modeling. Students in the Lipton group are exposed to a wide range of research techniques and areas. Broadly categorized, current projects in the Lipton group fall into the following areas:
Projects in this area stem from our own needs for new organic transformations or, more generally, from a recognized need in the organic chemistry community for a new method. In the former vein, we have recently developed new reagents for the guanylation of amines (i.e., their conversion to guanidines) [see ref. 17]. In the latter vein, we have developed a novel, cyclic dipeptide catalyst for an asymmetric version of the Strecker amino acid synthesis. This latter finding has led to a broad effort directed toward the use of cyclic dipeptide catalysts in asymmetric carbon-carbon bond forming reactions [see ref. 13]. This work has recently been highlighted in Chemical and Engineering News (April 28, 1997; p. 26-27; May 19, 1997; p. 38-40). We have initiated another broad effort in the area of reactions on solid supports, an area that has seen a tremendous growth in interest as a result of its application to the increasingly important subject of combinatorial synthesis [see ref. 15 and 22]. Our first efforts in this area were directed toward the synthesis of cyclic dipeptides for our studies of catalysie. Other projects involve the synthesis of peptidomimetics and macrocyclic lactams on a solid support.
Research in this area can be thought of as "drug design." Ongoing projects include the synthesis of inhibitors of the enzymes cyclophilin A (a peptidyl prolyl isomerase) and HIV-1 protease (essential for the replication of the HIV-1 virus and the pathogenesis of AIDS), and the synthesis of novel DNA-cleaving agents for the treatment of cancers, especially those leading to solid tumor formation. Projects of this type usually are designed using molecular mechanics calculations and tested "in house" after synthesis.
Peptidomimetics are those molecules designed to replace the amide bond linkage of normal peptides. Over the past 20 years, many possible replacements have been introduced: (E)-alkenes, thioamides, "azatides," sulfonamides, hydroethylenes, carbamates and ureas. While most of these functionalities bear a strong structural resemblance to the amide bond of peptides, they may adopt markedly different conformations than the parent system. Such a question is being examined using ab initio quantum mechanics calculations, molecular mechanics calculations and multidimensional NMR [see ref. 20]. In addition, we have recently developed a novel peptidomimetic (based on the replacement of the amide bond by a urea) that is now being tested for activity.
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Last modified July 24, 2006.