The studies concern principally lipid components, usually surface oriented, of Mycobacterium species, in which the lipids are inferred to have a role in antigenicity; in virulence or in attenuation; or which have unusual biological activities. A considerable attenuation in a select few M. tuberculosis strains has been associated with a concomitant phenotypic loss of ability in produce phthiocerol dimycocerosate (""""""""DIM"""""""") in culture. We seek to define the lesion in biosynthesis that is responsible for the loss and to interpret, if possible, its relevance to the change in virulence. A very fruitful synthesis program has provided us about a score of interesting and unusual analogs of trehalose dimycolate (cord factor, TDM) for most of which toxicity was assessed. These will now be tested in a syngeneic guinea pig tumor model for antitumor behavior to define the relations between structure, toxicity and antitumor activity. some essentially non-toxic TDM analogs may be candidates for clinical trials. Influence of these pseudo cord factors on the functionalities of mouse peritoneal macrophages will be studied. The results are expected to define specific physical and structural requirements for macrophage stimulation/activation. The studies can provide information as to whether any of the rigorously defined synthetic products might find practical use as immunomodulators. A number of important serologically active mycobacterial glycolipids or glycopeptidolipids are notoriously poor antigens. Sulfated analogs will be prepared and complexed with methylated bovine serum albumin to seek enhancement of antigenicity, but with the expectation that the specificity of the antibodies elicited by the complex will be essentially the same as stimulated by the (complexed) native glycolipids. We have developed a facile inexpensive synthesis of 3,6-di-O-methyl glucose, the principal specific carbohydrate moiety in the unique antigenic phenolic glycolipid (PGL-I) of Mycobacterium leprae. The synthesis will be exploited to prepare a variety of novel derivatives targeted for serving as inexpensive practical antigens for use in serological testing of sera for evidence of anti-PGL-I antibodies and therefore to detect infection with M. leprae.
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