Carbohydrate conjugates, hydrolysis

The products given by glycosidase enzymic hydrolysis of a precursor isolate depend not only upon the nature of the carbohydrate conjugating moiety but also on the specificity of the enzyme(s) and, therefore, the particular enzyme preparation used (Gunata et al. 1993 Williams 1993). 

Bob s research interests and knowledge across chemistry were great. Throughout his career he retained an interest in biomimetic chemistry, specifically the study of metal ion-promoted reactions and reactions of molecules activated by metal ion coordination. His early interests in carbohydrate chemistry inspired him to study metal ion catalysis of both peptide formation and hydrolysis as well as studies in inorganic reaction mechanisms. He was particularly interested in the mechanisms of base-catalyzed hydrolysis within metal complexes and the development of the so-called dissociative conjugate-base (DCB) mechanism for base-catalyzed substitution reactions at inert d6 metal ions such as Co(III). 

Monomeric carbohydrates in their cyclic form (furanoses and pyranoses) are hemiacetals, which, to become acetals, form 0-glycosyl conjugates. The C-atom C(l) that bears two O-atoms is the reactive, electrophilic center targeted by glycosidases. Nonenzymatic hydrolysis is also possible, although, as a rule, under physiological conditions of pH and temperature, the reaction is of limited significance. 

Hphe molecular mechanism of acid hydrolysis of glycosides is rather well understood today, much confusion being resolved now by the achievements of conformational analysis of carbohydrates (1,2). With regard to the three consecutive steps of reaction (cf. Figure 1)—Le., the formation of a conjugate acid by protonation of either one of the acetalic... 

Another limitation in the current analytical practices is that the vast majority of the studies focus on the nature of the sterols, but only a few on the characteristics on the conjugated compounds (fatty acids, carbohydrates, etc.). However, as these may have an effect on, for example, the rate of hydrolysis of these compounds in the gastrointestinal tract and other biochemical processes, the chemistry of the conjugated moieties should be analyzed in more detail. 

Figure 10 The stability of a freeze-dried monoclonal antibody/vinca alkaloid conjugate formulation. Desacetylvinblastine hydrazide is linked to the KSl/4 monoclonal antibody via aldehyde residues of the oxidized carbohydrate groups on the antibody. The formulation is conjugate/glycine/mannitol in a I I I weight ratio. Storage temperatures are 25°C and 40°C for samples with moisture contents of 1.4%, 3.0%, and 4.7%. ( ) Dimer formation. (A) Free vinca generation (hydrolysis). ( ) Vinca degradation. (—) Best fit to the WLF equation. (Reproduced with permission from [54].)...

Proteins are classified into two major types according to their composition. Simple proteins, such as blood serum albumin, are those that yield only amino acids on hydrolysis. Conjugated proteins, which are much more common than simple proteins, yield other compounds such as carbohydrates, fets, or nucleic acids in addition to amino acids on hydrolysis. 

Rich in both phase I (principally the cytochromes P450, catalyzing hydrolysis, reduction, and oxidation reactions) and phase II (catalyzing conjugation of xenobiotic molecules with hydrophilic moieties) biotransforming enzymes, the liver is the metabolic center of the body. In fact, most of the field of biochemistry is concerned with its metabolic reactions. The liver essentially converts ingested food into a balanced cell culture medium via metabolic interconversion of amino acids, carbohydrates, and lipids and synthesizes many substances that are subsequently exported for use in other areas of... 

Steroid saponins are composed of a steroid (C 27) nucleus with carbohydrate molecules. The steroid saponins on hydrolysis give aglycones known as saraponins. These types of saponins have anti-fungal activity. In animal models they have shown to inhibit smooth muscle activity. Steroid saponins are excreted after conjugation with glucouronic acid. They are used as raw material for biosynthesis of cortical steroid dmgs. 

In some examples, the stereochemistry of radical reactions was controlled by chiral carbohydrate auxiliaries. As a radical counterpart to the ionic conjugate additions discussed above, Garner et al. [169] prepared carbohydrate linked radicals that were reacted with a,P-unsaturated esters. The radical precursor, the carboxylic acid 256, generated by the addition of ( Sj-methyl lactate to tri-O-benzyl-D-glucal and subsequent ester hydrolysis, was decarboxylated by Barton s procedure (Scheme 10.84) [170]. Trapping of the chiral radical 258 with methyl acrylate furnished the saturated ester 259 in 61% yield and with high diastereoselectivity (11 1). The auxiliary caused a preferential addition to the si-facQ of radical 258, probably due to entropic effects. The ester 259 was transformed in acceptable yield to the y-butyrolactone 261 by reductive removal of the thiopyridyl group followed by acid hydrolysis. 

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