Bandicoots and bilbies (Peramelemorphia) represent a distinct lineage within the marsupial adaptive radiation, which despite several curious anatomical traits has received little morphological attention. Many bandicoot species (family Peramelidae) dig for subterranean food, while bilbies (family Thylacomyidae) employ their forelimbs to dig extensive burrow systems for shelter. In the current study, dissections of the southern brown bandicoot (Isoodon obesulus) (n = 7) and greater bilby (Macrotis lagotis) (n = 4) provide the first anatomical descriptions of forelimb musculature in these species. The anatomical arrangement of forelimb muscles in I. obesulus and M. lagotis differs from that of other marsupials and corresponds to the aclaviculate pectoral girdle and modified arrangement of digits in the study species. Comparative and functional interpretations indicate that the forelimb of I. obesulus is well equipped for scratch digging and demonstrates muscular modifications in order to generate large out-forces. The bones of the forelimb, and in particular the antebrachium, are relatively short, stout bones, improving both their resistance to mechanical forces and providing a mechanical advantage via a reduced out-lever length. There has been an increase in the absolute volume of muscles employed during digging, thereby increasing the magnitude of the in-force. Increased in-lever lengths have been achieved via the migration of muscle insertions, including the elongate olecranon for the insertion of the m. triceps brachii, and the distal migration of the humeral attachments of the teres major, latissimus dorsi and superficial pectoral muscles.

Conjugate vaccines composed of polysaccharides or oligosaccharides covalently linked to immunogenic proteins successfully overcome the limitations of pure polysaccharide antigens, which are classical T-cell-independent antigens.[1] To date, the use of oligosaccharides to provide the recognition element of such conjugate vaccines has largely been limited to experimental, proof of concept investigations, whereas polysaccharide conjugates are successfully employed in efficacious vaccination strategies against life-threatening bacterial infections. [1][2][3] Intensive efforts are directed toward the synthesis and evaluation of glycopeptide and glycolipid vaccines that present tumour-associated carbohydrate antigens, [4][5][6] the epitopes of which may contain glycosidic linkages that are potentially susceptible to endogenous glycosyl hydrolases, for example, ganglioside-specific plasma-membrane sialidase. [7][8][9] Such structural features include, but are not limited to, terminal sialyl residues, the loss of which would destroy crucial recognition elements. A method for the formation of glycosidic linkages that are resistant to enzymatic or acid hydrolysis in vivo has been proposed; C-glycosides are one class of compound that has received attention.[10-12] Herein we present data for four distinct antigen systems that show, for the first time, conjugate vaccines constructed from oligosaccharides that contain a thioglycosidic linkage function as well as antigens that induce antibodies specific for O-linked oligosaccharides.The choice of sulfur (over atoms such as carbon) to replace oxygen at the glycosidic center was based on three considerations: the ease of synthesis, [13] the existence of welldocumented examples with a similar conformational preference about the thioglycosidic and aglyconic bonds both when in solution and when complexed with a protein, [14][15][16][17] and significantly lower susceptibility to enzymatic and acid hydrolysis. [18,19] Although the sulfur-carbon bond is longer than the carbon-oxygen single bond, the CÀSÀC bond angle is significantly smaller than the CÀOÀC angle, which often results in relatively small differences between the position of the carbon atoms of the glycosidic linkage.[20] However, the longer bonds and weaker stereoelectronic effect that result when oxygen is replaced with sulfur allow substantially greater flexibility.This flexibility creates a potential obstacle to the use of thioglycoside immunogens. S-Glycosidic bonds are less constrained than the corresponding O-glycosides and can access the higher energy anti conformation in the unbound and bound state more readily. In the search for effective protective carbohydrate epitopes, it remains an open question as to whether such conformational flexibility would preclude the effective use of antigenic determinants that contain metabolically stable S-linkages. Although the structural similarity of O-and S-linked oligosaccharides is critical to this concept, their differences may also identify S-glycosides as non-self antigens ...

Pathogenic organisms or oncogenically transformed cells often express complex carbohydrate structures at their cell surface, which are viable targets for active immunotherapy. We describe here a novel, immunologically neutral, linker methodology for the efficient preparation of highly defined vaccine conjugates that combine complex saccharide antigens with specific TH-cell peptide epitopes. This novel heterobifunctional approach was employed for the conjugation of a (1-->2)-beta-mannan trisaccharide from the pathogenic fungus Candida albicans as well as the carbohydrate portion of tumor-associated ganglioside GM2 to a TH-cell peptide epitope derived from the murine 60 kDa self heat-shock protein (hsp60). Moreover, the linkage chemistry has proven well suited for the synthesis of more complex target structures such as a biotinylated glycopeptide, a three component vaccine containing an immunostimulatory peptide epitope from interleukin-1 beta (IL-1 beta), and for the conjugation of complex carbohydrates to carrier proteins such as bovine serum albumin.

Analogues of GM3 and GM2 gangliosides were chemoenzymatically synthesized on a multifunctional ceramide-type tether designed to facilitate diverse strategies for glycoconjugate synthesis. The truncated ceramide aglycon maintains the stereogenic centres of natural ceramide while avoiding extensive hydrophobicity that can hamper synthesis and purification of the glycolipids. Tetanus toxoid and BSA glycoconjugates of these two gangliosides were prepared for immunization of mice, and for solid phase assays to screen for ganglioside-specific antibodies. Inhibition experiments showed that antibodies generated by tetanus toxoid conjugates of GM3 and GM2 exhibited specificity for the carbohydrate epitope and the stereogenic centres of the ceramide.