Outer-Core Polysaccharides

The outer region of the core oligosaccharide affects the innate immune responses in the normal host. For example, patients with cystic fibrosis are hypersusceptible to chronic airway infections, particularly with Pseudomonas aeruginosa [127], It was shown that the outer-core region of the LPS of P. aeruginosa influences a critical step 

Glycoforms of the outer-core structure of P. aeruginosa CPS repeating units of Strep, pneumoniae 19F and 19A 

FIGURE 14.4 Outer-core polysaccharides and CPS as synthetic targets. Man, mannose PMP, p-methoxyphenyl Rha, rhamnose. 

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Fig. 6 An initial treatment (A) with DT-mutant decorated with the inner core mimic Hep2KD02 will raise antibody (B) against the inner-core carbohydrate portion of bacterial polysaccharide. Successively, y-cyclodextrin are used to inhibit Wza, which is the outer core polysaccharide transporter, exposing the inner core to the antibody and generating the immune response (C) to kill the bacteria. ...

I 0-SPECIFIC POLYSACCHARIDE OUTER CORE INNER CORE LIPID A... 

LPS is located in the outer membrane of Gram-negative bacteria and composed of 0-antigen polysaccharide, core polysaccharide, and lipid A. It was found that lipid A is the key compo-... 

Lipopolysaccharides are considered to be composed of three segments, lipid A, the core polysaccharide and the antigenic side chains. The core polysaccharide, in turn, has an inner region (which is linked to lipid A) called the backbone sequence and an outer core to which the antigen chains are attached. The lipopolysaccharides of Salmonella typhimurium are the best known and they will be used here as examples. 

Gram-negative bacteria have a cell envelope containing two membranes, with the outer membrane having lipopolysaccharide in its outer leaflet. Lipopolysaccharide is complex and consists of four parts. On the outside is the O-antigen which is a polysaccharide of variable structure. This is attached to a core polysaccharide which is in two parts, an outer core and a backbone. The backbone is connected to a glycolipid, called lipid A, through a... 

Gram-negative bacteria contain lipopolysac-charide in the outer membrane of their cell envelope. The lipopolysaccharide is a complex polymer with four parts. On the outside is a polysaccharide of very variable structure which is then attached to a core polysaccharide which itself is divided into an outer core and a backbone. The outer cores are variable in composition but the link which connects the backbone to lipid A is usually composed of 3-deoxy-D-manno-octulosonic acid (KDO). The presence of KDO (Fig 3.3) is often used as a marker for lipopolysaccharide or outer membrane. 

KDO has chemical properties similar to those of neuraminic acid as it has a carboxylate group, a 3-deoxy group, and a similar biosynthesis (see Chapter 10). The monosaccharide composition, sequence, and linkages, along with the position of attachment of phosphate and ethanolamine pyrophosphate substituted onto the heptose residues of the core polysaccharide have been determined [53-58] and are shown in Fig. 9.16C. The fatty acids in the lipopolysaccharide participate in the formation of a lipid bilayer for the outer membrane. The carbohydrate is hydrophilic and is located on the outer faces of the lipid bilayer membrane. The O-antigen polysaccharides and other capsular polysaccharides are attached to position-4 of the next to last monosaccharide residue, a-D-glucopyranose of the core polysaccharide. 

Full Outer Inner polysaccharide core core... 

Vimses are one of the smallest biological entities (except viroids and prions) that carry all the iaformation necessary for thek own reproduction. They are unique, differing from procaryotes and eucaryotes ia that they carry only one type of nucleic acid as genetic material, which can be transported by the vims from one cell to another. Vimses are composed of a shell of proteki enclosing a core of nucleic acid, either ribonucleic acid (RNA) or deoxyribonucleic acid (DNA), that codes for vkal reproduction. The outer shell serves as a protective coat to keep the nucleic acid kitact and safe from enzymatic destmction. In addition to thek proteki coat, some vimses contain an outer covering known as an outer envelope. This outer envelope consists of a Hpid or polysaccharide material. 

L-glycero-mannoheptose. The polysaccharide component of LPS may be divided into several structural domains. The inner (core) domains vary relatively little between LPS molecules isolated from different Gram-negative bacteria. The outer (O-specific) domain is usually bacterial strain-specific. 

For chemotherapeutics to be effective against Gram-negative bacteria requires a balance between hydrophilic and hydrophobic properties. The reason for this is the characteristic construction of the bacterial cell wall, with an outer hydrophilic core, rich in polysaccharides, and a hydrophobic phospholipid bilayer. Only very small and hydrophilic drug molecules up to 600 Da can diffuse through membrane pores [63, 64],... 

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