Acyl residue

The results of more recent investigations by Blicke with Maxwell and with Kaplan covering a wide range of basic components and of acyl residues, do not lend themselves to a simple generalisation. The basic components were mainly dialkylamino-derivatives of aliphatic hydrocarbons from ethane to pentane, e.g.,. CHj. CHj. NMcj to. CHj. CMcj. CHj. NEtj, and similar but shorter series of derivatives of piperidine (CgHjoN), morpholine, e.g.,. CHj. CHj. NC HgO, and methylcj/clohexylamine... 

Stereoisomerism in either the alkamine nucleus or the acyl residue has a considerable effect on the pharmacological action of the tropeines and cocaines. Differences in activity of tropine and i/i-tropine and their benzoyl derivatives have been mentioned already, and there seems to be a consensus of opinion that the i/i-cocaines (alkyl- or aryl- acyl esters of 0-ecgonine) are less toxic and more potent local anfesthetics than the corresponding cocaines, derived from 1-ecgonine. ... 

The acyl residue controls the formation and stability of the carbonium ion. If the carbonium ion is destabilized (by electron withdrawing groups), then cyclization to the phenanthridine nucleus will be sluggish. The slower the rate of cyclization, the greater the chance of side reactions with the cyclization reagent. Therefore, the yield of the phenanthridine will depend on the relative rates of cyclization and side reactions, which is controlled by the stability of the carbonium ion. 

It was almost immediately recognised that the deacylated product, 7-aminocephalosporanic add (7-ACA, Figure 6.16), would be of similar importance as was 6-APA in the development of new penidllins. However, 7-ACA, the cephalosporin equivalent of 6-APA, could not be found in fermentations of Cephalosporin acremonium. In Figure 6.15 we have shown that penicillin acylase hydrolyses the acyl residue from natural cephalosporins. Up to a point this is true. These acylases will, however, only work with a limited range of acyl residues. It now seems that nature does not provide for acylases or transacylases that have the capacity to remove or change the D-a-aminoadipyl side chain of cephalosporin C efficiently in a single step. Widespread search for such an enzyme still remains unsuccessful. 

Derivatives play an essential part in almost all f.a.b.-m.s. studies of carbohydrates. They facilitate spectral interpretation (see Sections IV-VI), improve sensitivity (see Section 11,6), permit the analysis of salty samples (see later), allow unambiguous sequencing (see Section V,2), confirm the presence of cyclic structures (see Section VI,S), enable spectra to be obtained from very large molecules (see Section III,4), and help in the location of O-acylated residues in oligosaccharides (see Section V,S). 

Fig. 1.8 The conformational behavior of the two amino acyl residues of carnosine (1 2 versus plot) as simulated for 5 ns in water (in blue) or when bound to carnosinase (in...

A potential liability associated with such reductive hydroacylations resides in the fact that only one acyl residue of the symmetric anhydride is incorporated into the coupling product. For more precious carboxylic acids, selective acyl transfer from mixed anhydrides is possible. Mixed anhydrides derived from pivalic acid are especially convenient, as they may be isolated chromato-graphically in most cases. In practice, mixed anhydrides of this type enable completely branch-selective hydroacylation with selective delivery of the aromatic and a,()-unsalurated acyl donors (Scheme 19). 

The third acyl residue is transferred onto diglyceride by means of diglyceride acyltransferase... 

Lipid A contains primary fatty acids directly linked to hydroxyl and amino groups of the backbone, and secondary fatty acids bound to hydroxyl groups provided by the primary acyl residues. The number of carbon atoms of primary and secondary fatty acids is, in the majority of lipid A studied, in the range of 10 to 18. They are, in general, saturated, even-numbered, and straight-chain fatty acids and in only few cases, are unsaturated, odd-numbered, and iso- and ante-iso branched derivatives present in molar amounts. 

Takayama and coworkers (60) introduced the h.p.l.c. separation technique for such amphiphilic molecules as lipid A, and in earlier experiments they applied paired-ion reverse-phase h.p.l.c. for the preparation of homogeneous fractions deriving from 4,-monophosphated lipid A of S. typhimur-ium. The purified preparations obtained were suitable for f.a.b. - m.s. analysis. However, monophosphated lipid A isolated in this way expressed a considerable heterogeneity with respect to the number and location of 0-acyl residues (60). In order to further improve the purification procedure, as well as to obtain lipid A derivatives suitable for n.m.r. spectroscopy, Qureshi et al. (174) prepared the dimethyl phosphate derivative of S. minnesota (R595) lipid A, which, after purification by reverse-phase h.p.l.c. (C18), could be analyzed by1 H-n.m.r. The n.m.r. spectrum of, for example, the heptaacyl lipid A dimethyl monophosphate fraction, unequivocally revealed 0-acyl substitution [14 0(3-OH)J at position 3 and a free hydroxyl group at position 4 of GlcN(I). 

As the preceding sections show, the term lipid A does not denote a defined molecular entity but rather a family of structurally closely related but not identical phosphoglycolipids. Their structures may differ in the type and number (one or two) of HexpN residues present in the backbone by the number, location, nature, size, and linkage of acyl residues by the nature of phosphate substituents and finally by the degree of phosphorylation of the backbone. Lipid A components of different bacterial origin are classified in the present article on the basis of structural variations. 

These reactions were demonstrated with pure enzymes or various biological media such as human peripheral blood mononuclear cells uninfected or infected with HIV. In the latter case, highly promising antiviral results were obtained. Furthermore, a variety of amino acyl residues, carboxylic acid ester moieties, and aryl substituents X have been reported. 

Fig. 5. Acyl residues encountered in fungal hydroxamate siderophores...

Parentheses indicate that the position of the residues is not certain. For the designation of the acyl residues see Fig. 5. Where the chirality of Ala or Ser was determined it was found to be L... 

Huschka HG, Jalal MAP, van der Helm D, WinkelmannG (1986) Molecular Recognition of Siderophores in Fungi Role of Iron-surrounding V-Acyl Residues and the Peptide Backbone During Membrane Transport in Neurospora crassa. J Bacteriol 167 1020... 

Testosterone (T.) derivatives for clinical use. T. esters for im. depot injection are T. propionate and T. heptanoate (or enanthate). These are given in oily solution by deep intramuscular injection. Upon diffusion of the ester from the depot, esterases quickly split off the acyl residue, to yield free T. With increasing lipophilicity, esters will tend to remain in the depot, and the duration of action therefore lengthens. A T. ester for oral use is the undecanoate. Owing to the fatty acid nature of undecanoic acid, this ester is absorbed into the lymph, enabling it to bypass the liver and enter, via the thoracic duct, the general circulation. 17-0 Methyltestosterone is effective by the oral route due to its increased metabolic stability, but because of the hepatotoxicity of Cl 7-alkylated androgens (cholestasis, tumors) its use should be avoided. Orally active mesterolone is 1 a-methyl-dihydrotestosterone. Trans-dermal delivery systems for T. are also available. 

Coenzyme A (see also p. 106) is a nucleotide with a complex structure (see p. 80). It serves to activate residues of carboxylic acids (acyl residues). Bonding of the carboxy group of the carboxylic acid with the thiol group of the coenzyme creates a thioester bond (-S-CO-R see p. 10) in which the acyl residue has a high chemical potential. It can therefore be transferred to other molecules in exergonic reactions. This fact plays an important role in lipid metabolism in particular (see pp. 162ff), as well as in two reactions of the tricarboxylic acid cycle (see p. 136). 

Fats are esters of the trivalent alcohol glycerol with three fatty acids. When a single fatty acid is esterified with glycerol, the product is referred to as a monoacylglycerol (fatty acid residue = acyl residue). 

The three acyl residues of a fat molecule may differ in terms of their chain length and the number of double bonds they contain. This results in a large number of possible combinations of individual fat molecules. When extracted from biological materials, fats always represent mixtures of very similar compounds, which differ in their fatty acid residues. A chiral center can arise at the middle C atom (sn -C-2) of a triacylglycerol if the two external fatty acids are different. The monoacylglycerols and diacylglycerols shown here are also chiral compounds. Nutritional fats contain palmitic, stearic, oleic acid, and linoleic acid particularly often. Unsaturated fatty acids are usually found at the central C atom of glycerol. 

The other phospholipids can be derived from phosphatidates (residue = phosphatidyl). Their phosphate residues are esterified with the hydroxyl group of an amino alcohol choline, ethanolamine, or serine) or with the cyclohexane derivative myo-inositol. Phosphatidylcholine is shown here as an example of this type of compound. When two phosphatidyl residues are linked with one glycerol, the result is cardiolipin (not shown), a phospholipid that is characteristic of the inner mitochondrial membrane. Lysophospholipids arise from phospholipids by enzymatic cleavage of an acyl residue. The hemolytic effect of bee and snake venoms is due in part to this reaction. 

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