Cord factor structure

The chemical synthesis of derivatives and emalogs has long coimnanded much interest, as such compounds are required for the study of structure—activity relationships in the action of trehalases (23,28), may serve as substitutes for 51 in the synthesis of cord-factor analogs to be used as probes in the field of mycobacterial biochemistry (29, 30), and could possibly prove to possess interesting properties as enzyme inhibitors or antibiotic agents. 

Bacteria also contain a very rich variety of glycolipids with unusual structures. Lipid A13 is the site of attachement of the 0-specific chain of Gram (-) bacteria, which constitutes the antigenic lipopolysaccharide [87]. Other members of this family can be quoted, for example glycosyl glycerophospholipids in which the carbohydrate and glycerol moieties are linked by a phosphodiester bond (e.g. GPI anchor 14) [88] or carbohydrate esters (e.g. cord-factor of mycobacteria 15). 

Chemical Structure of Cord Factor.—A first important clue to the... 

As soon as structure (4) was certain for cord factor, efforts were made to prepare 6,6 -diesters of trehalose with mycolic acids, so as to confirm struc-... 

Variations of the Structure of Natural Cord-factor in Different Strains. —It is known that different strains frequently contain a different assortment of mycolic acids. Thus, it is not astonishing that cord factor of different strains sometimes contains different mycolic acids. It was found that cord factor of a streptomycin-resistant strain of H37-Rv and of the BCG strain contains a methoxyl-free 3, x-dihydroxymycolanoic acid C87H174O4 5 CHj, whereas the virulent, human strain Br vannes contains a cord factor wherein the mycolic acid is a 3-hydroxy-x-methoxy-mycolanoic acid C88H176O4 5 CH2. 

Considerable interest has been shown in the structure and occurrence of cord factors. Amongst the biological properties examined was their effect on mitochondria. 

The cell walls of M. lepraemurium have been harvested from the livers of moribund rats that had been infected with the above organism. The walls contained a cord factor (oa-trehalose-6,6-dimycolate) that was similar in structure to the well-characterized cord factor from M. tuberculosumThis is the first unequivocal identification of a cord factor as a product of in vivo derived mycobacteria. 

The purification procedure of 6,6 -esters of OMf-trehalose from Coryne-bacterium diphtheria has been modified and the products were analysed by m.s. of the permethylated derivative.The constituent fatty acids have been extensively examined and the detailed structure of the major acids have been confirmed by a variety of techniques. Novel glycolipids in the cord factor fraction from C. diphtheria were a 6,6 -bis(3-oxo-acyl)-o a -D-trehalose and a 6, 6 -mixed ester of aa-trehalose with the 3-oxo-acyl group and a corynomycolic acid. The metabolic implications of these structural studies suggest that condensation of the common fatty acids by a Claisen-like process via the oxo-ester pathway may not be the only pathway for the synthesis of the cord factors. 

Puzo G, Tissie G, Lacave C, Aurelle H, Prome JC. Structural determination of cord factor from a Corynebacterium diphtheriae strain by a combination of mass spectral ionization methods field desorption cesium cationization and electron impact mass spectrometry studies. Biomed Mass Spectrom. 1978 5 699-703. 

The structure of the cord factor from Mycobacterium smegmatis has been confirmed as (j ,a trehalose 6,6 -dimycolate (CieeHajsOis). The a,a trehalose was identified by paper chromatography and the positions of ester linkages at 0-6 and 0-6 was established by C n.m.r. spectroscopy. 

Stimulation of free nerve endings known as nociceptors is the first step leading to the sensation of pain. These receptors are found in both somatic and visceral structures and are activated by mechanical, thermal, and chemical factors. Release of bradykinins, K1, prostaglandins, histamine, leukotrienes, serotonin, and substance P may sensitize and/or activate nociceptors. Receptor activation leads to action potentials that are transmitted along afferent nerve fibers to the spinal cord. 

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