Fatty acyl amides, classes

Identification and structural characterization of an unknown class of substrates for FAAH. (A) By high-resolution mass spectrometry, the high-accuracy mass measurements of a compound of this class gives an exact mass of 446.3310 that corresponds to a molecular formula of C24H48N04S. (B) By MS/MS analysis, the structure of this compound is assigned as the C24 0 fatty acyl amide of taurine (NAT). Reproduced from Saghatelian A., Trauger S.A., Want E.J., Hawkins E.G., Siuzdak G. and Cravatt B.F., Biochemistry, 43,14332-14339, 2004, with permission. 

These experiments show altogether that the unknowns are amides of taurine from several fatty acids. Therefore, this new class of endogenous substrates of FAAH corresponds to fatty acyl amides of taurine (NAT) with very long-chain fatty acids. The structure of this new class of substrates of FAAH is confirmed by chemical synthesis and comparison of retention times and mass spectra obtained for these synthetic products with those of the natural products. 

SLs are also polar cell membrane lipids, but they are typically present in much lower concentration than PLs. Soybeans are a relatively rich source of SLs (Vesper et al., 1999), and ceramides and cerebrosides are the primary SL classes in soybeans. SLs contain a sphingoid long-chain (CIS) drhydroxy base and an a-hydroxy fatty acyl chain that is linked to the base by an amide bond. The main soybean ceramide molecular species is a trihydroxy base (4-hydroxy-trans 8-sphingenine) V -acylated with a-hydroxy lignoceric acid (C24 0). The main soybean cerebroside molecular species is a dihydroxy base trans A-trans 8-sphingediene) V acylated with a-hydroxy palmitic acid. The general molecular structures of ceramide and cerebroside are shown in Fig. 10.4. 

Other major lipid classes in the fatty acyl category include fatty add esters, such as wax monoesters and diesters and the lactones. The fatty ester class also has subclasses that include important biochemical intermediates, such as fatty acyl thioester-CoA derivatives, fatty acyl thioester-acyl carrier protein (ACP) derivatives, fatty acyl carnitines (esters of carnitine), and fatty adenylates, which are mixed anhydrides. Fatty alcohols, fatty aldehydes, and fatty amides represent further subclasses, the last sometimes showing interesting biological activities in various organisms. 

Saccharolipidsm, where fatty acids are linked in ester and amide linkages directly to sugar molecules. This is a relatively small class of molecules, best described in bacteria and plants. The most well known of these are the acylated glucosamine precursors of the lipid A component of the endotoxin thought to be responsible for the toxicity of Gram-negative bacteria. A simple monosaccharide precursor. Lipid X, is shown in Table 3.1. 

The Chemical Synthesis of Peptides Carboxylic acids and acyl derivatives of the carboxyl functional group are very important in biochemistry. For example, the carboxylic acid functional group is present in the femily of lipids called fatty acids. Lipids called glycerides contain the ester functional group, a derivative of carboxylic acids. Furthermore, the entire class of biopolymers called proteins contain repeating amide functional group linkages. Amides are also derivatives of carboxylic acids. Both laboratory and biochemical syntheses of proteins require reactions that involve substitution at activated acyl carbons. 

One important milestone in our research is the design and development of new amino acid-based surfactants with antimicrobial properties, which mimic natural amphiphilic cationic peptides [42,43]. To this end, Lys and Arg derivatives of long-chain A -acyl, COO-ester, and A-alkyl amide have been prepared. In particular, the A -acylarginine methyl ester derivatives series 1 (Scheme 1) have turned out to be an important class of cationic surface active compounds with a wide bactericidal activity, high biodegradability, and low toxicity profile. We have shown that essential structural factors for their antimicrobial activity include both the length of the fatty residue (akin with their solubility and surface activity) and the presence of the protonated guanidine function [43,44]. 

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