Amino acids small molecules synthesised from

Table 8.4 Some small nitrogen-containing molecules synthesised from amino acids...

Interferons [alFN, piFN and ylFN]. Interferons are a family of glycosylated proteins and are cytokines which are produced a few hours after cells have been infected with a virus. Interferons protect cells from viral infections and have antiviral activities at very low concentrations ( 3 x 10 M, less than 50 molecules are apparently sufficient to protect a single cell). Double stranded RNA are very efficient inducers of IFNs. There are three main types of IFNs. The aIFNs are synthesised in lymphocytes and the piFNs are formed in infected fibroblasts. The a and P families are fairly similar consisting of ca 166 to 169 amino acids. Although ylFNs are also small glycosylated proteins (ca 146 amino acids), they are different because they are not synthesised after viral infections but are produced by lymphocytes when stimulated by mitogens (agents that induced cell division). 

Marine sponges contain a host of bioactive compounds, particularly small molecules, and also contain a range of peptides that are non-ribosomally synthesised, often containing non-native amino acids. However, there are examples of peptides of ribosomal origin, including, for example, asteropine A isolated from the sponge Asteropus simplex.133 This peptide comprises 36 residues and three disulphide bonds. It has potent sialidase inhibitory activity and thus has applications in the design of novel viral inhibitors. Structural analysis of asteropine A with NMR spectroscopy revealed a cystine-knot motif, similar to that already described for plant toxins. This observation emphasises the fact that the cystine-knot motif is extremely prevalent in disulphide-rich peptides.134 Asteropine A, discovered in 2006, was the first reported cystine-knot peptide isolated from marine invertebrates other than from cone snails, which are described in more detail below. 

More recent examples of biomimetic synthesis are the syntheses of thebaine [11] and usnic acid [12], as well as strychnine [13], morphine alkaloids [11] [14] and a great number of terpenic compounds [15]. On the other hand, hypothetic prebiotic considerations may also simplify tremendously the synthetic plans. Such is the case, for example, of the work of Eschenmoser on vitamin B12 who, after synthesising it in collaboration with Woodward by a linear sequence of almost fifty steps [16], investigated the prebiotic origen of this complex molecule. The experimental work undertaken in this direction demonstrates that the amount of "external instruction" required for "self-assembling" the different structural elements present in this molecule is surprisingly small. This fact could eventually lead to a very simple synthesis of vitamin Bj2 starting from a-amino nitriles which would involve only a few steps [17]. 

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