Prof. Israel Schechter
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1935
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2012
Israel Schechter first studied the active site of enzymes (proteases) discovering that their size is larger that expected, with important interactions in regions remote from the catalytic site allowing high binding energy of enzyme-inhibitor complexes. This led to rational design of inhibitors developed at 1990th into drugs against HIV (inhibitors of virus proteases) and revolutionized AIDs disease turning a lethal into a chronic disease. Other drugs were against hypertension, congestive heart failure, diabetes, cancer (methotrexate), bacteria (antibiotics), anti-viral (relenza) but also Viagra.
The Schechter-Berger model of the active site of enzymes divided into subsites (1967) became a milestone in enzymology and a template for drug design. His studies on the antibody combining site (1967) revealed a region of four subsites of independent Interactions being just additive, i.e., ligand’s binding energy was the sum of binding energy attained in each subsite. Israel also studied the biological aspects of the immune response focusing on cellular localization of antigen in relation to antibody producing cells. Other studies focused on immunological tolerance, antigenic competition, the role of antigen conformation on immunogenicity as well as the development of skin grafts with decreased immunogenicity and increased resistance to infection for the treatment of burnt patients. He also studied the molecular biology of schistosome, the cause of bilharzia., in collaboration with Egyptian scientists. Back in 1973 a major attention was devoted to the evolution of antibody diversity with the primary goal of isolating an immunoglobulin (Ig) gene. He was the first one to isolate pure mRNA encoding for a single protein (which could be translated to the first gene). He developed a general procedure based on the specific immune precipitation of polysomes engaged in the synthesis of a given molecule – here the Ig. The mRNA which was translated into the Ig precursor containing a signal peptide of marked hydrophobicity while intracellular but cleaved upon secretion, later identified as a property of other proteins as well