Other lysine derivatives

The -amino groups of lysyl residues serve as attachment sites of a number of coenzymes in proteins (e.g. biotin in pyruvate carboxylase, pyridoxal phosphate in phosphorylase, lipoic acid in lipoate acetyl-transferase) and form covalent intermediates in several enzymic reactions (e.g. transaldolase, aldolase, etc.). Discussion of all of these naturally-occuring derivatives of lysine will not be attempted in this treatise, but the investigator using chemical modification of proteins should be aware of their possible presence and effect on the results of his experiments. It should be noted that e-N-phospholysine has been reported in nucleoside diphosphate kinase (Walinder 1968). 

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Other lysine-derived alkaloids known as coccinellines (42-47) occur in many members of the family Coccinellidae (ladybugs or ladybird beetles) (Fig. 29.15). Many of these insects are also wamingly colored. Cryptic members of the same groups usually do not contain the alkaloids (Jones and Blum, 1983). These alkaloids also have been isolated from a soldier beetle, Chauliognathus and from the boll weevil Anthonomus grandis. Coccinellines are highly repellent to... 

The relationship between anemone fish, Amphiprion sp., and their sea anemone partners are regulated by alkaloids from the sea anemone. Amphiprion perideraion is attracted to the sea anemone Radianthus kuekenthali by the simple lysine-derived alkaloid amphikuemin (Fig. 12.6 Murata etal, 1986). Other simple alkaloids, aplysinopsin and dihydroaplysinopsin, also attract A. perideraion, regulate its swimming rate and induce their species-specific partnership. A related anemone fish, Amphiprion ocellaris, is attracted to the sea anemone Stoichactis kenti by tyramine (Fig. 12.6) and tryptamine induces searching by the fish (Murata etal, 1986). 

It is lysine derivative of enalaprilat. Mechanism of action is same as other ACE inhibitors. After oral administration it is absorbed incompletely and slowly. 

Enalapril is an oral prodrug that is converted by hydrolysis to a converting enzyme inhibitor, enalaprilat, with effects similar to those of captopril. Enalaprilat itself is available only for intravenous use, primarily for hypertensive emergencies. Lisinopril is a lysine derivative of enalaprilat. Benazepril, fosinopril, moexipril, perindopril, quinapril, ramipril, and trandolapril are other long-acting members of the class. All are prodrugs, like enalapril, and are converted to the active agents by hydrolysis, primarily in the liver. 

The search for other amino acid-based catalysts for asymmetric hydrocyanation identified the imidazolidinedione (hydantoin) 3 [49] and the e-caprolactam 4 [21]. Ten different substituents on the imide nitrogen atom of 3 were examined in the preparation, from 3-phenoxybenzaldehyde, of (S)-2-hydroxy-2-(3-phenoxy-phenyl)acetonitrile, an important building block for optically active pyrethroid insecticides. The N-benzyl imide 3 finally proved best, affording the desired cyanohydrin almost quantitatively, albeit with only 37% enantiomeric excess [49]. Interestingly, the catalyst 3 is active only when dissolved homogeneously in the reaction medium (as opposed to the heterogeneous catalyst 1) [49]. With the lysine derivative 4 the cyanohydrin of cyclohexane carbaldehyde was obtained with an enantiomeric excess of 65% by use of acetone cyanohydrin as the cyanide source [21]. 

Decodine derived from [l-14C]cadaverine showed a distribution of label identical to that of the lysine-derived samples. Activity was equally divided between C-9 (j8-alanine) and C-5 (2-piperydylacetate minus -alanine). In decodine, into which AC - Cjpiperideine was incorporated, the label was confined to C-9. This was consistent with the established evidence that the double bond in A -piperideine does not migrate from one side of the nitrogen to the other (89, 90). 

We have recently reported that the low molecular weight poly-L-lysine derivatives are present in a random coil structure, in spite of the high content of the base, and are unable to form the polymer complex79. The formation of such a complex was not observed for the polyMAOA low molecular weight PLL-T system. This fact indicates that polyMAOA and PLL-T occurring in a random coil structure are incompatible and unable to penetrate each other. 

The stability and stoichiometry of the con lex between polymers containing nucleic add bases are affected by the con atibility of the different base-base distances in the polymers, and also by the mutual penetration ability between the main chains. In the polyMAOA-polyMAOT system, for example, intramolecular base-base distances in each polymer are compatible and these polymers are able to penetrate each other Poly-L-lysine derivatives and vinyl polymers are apparently incompatible. This situation alone would lead to unstable complex formation where the overall stoichiometry would not be simple and thus could not reflect the stoichiometry on the binding site. 

Homocitrulline elutes from most analyzer columns just prior to valine. Alternatively, the unreacted lysines can be converted under denaturing conditions to other acid-stable derivatives (homoarginine, methyl-lysines, carboxymethyllysines) which can be quantitated after acid hydrolysis (above and 2.12). The homocitrulline content can then be assumed to be the difference between the total lysine content and the content of the acid-stable derivative. Alkaline hydrolysis of carbamylated proteins gives quantitative conversion of homocitrulline to lysine (Stark and Smyth 1963), and this can be used to check the homocitrulline content of the protein in which the other lysines have been converted to another derivative that does not give lysine by alkaline hydrolysis (see also 3.I.2.I.). 

Hi) N -Methyllysines. Monomethyllysine was first observed in the flagellum protein of S. typhimurium by Ambler and Rees (1959). Since then, mono-, di-, and trimethyl derivatives of lysine have been found in a wide variety of proteins (see Paik and Kim, 1975). The methyl groups, as in other such derivatives, arise from S-adenosylmethionine, but the functional importance of the modifications remains obscure. Numerous procedures have been developed for their identification and quantification (Glazer et a/., 1975 Paik and Kim, 1975). 

The representative 2-alkenal adducts are summarized in Figure 6.4. The reactions of lysine with 2-alkenals have been mainly studied with acrolein, crotonaldehyde, and 2-nonenal. Similar to other a,P-unsaturated aldehydes, acrolein selectively reacts with the cysteine, histidine, and lysine residues of proteins. The primary products are their 3-substituted propanals (1) (Figure 6.4a). These p-substituted propanals or Schiff s base crosslinks had been suggested as the predominant acrolein-lysine adducts however, the major product formed upon the reaction of acrolein with a protein was identified to be a novel lysine product, A -(3-formyl-3,4-dehydropiperidino) lysine (FDP-lysine) (2), which requires attachment of two acrolein molecules to one lysine side chain (Uchida et al, 1998b). This and the fact that crotonaldehyde also forms a similar FDP-type adduct, A -(2,5-dimethyl-3-formyl-3,4-dehydropiperidino) lysine (dimethyl-FDP-lysine) (Ichihashi et al., 2001), suggest that this type of condensation reaction is characteristic of the reaction of 2-alkenals with primary amines. Indeed, upon reaction with a lysine derivative, other 2-alkenals, such as... 

Nicotine is the main alkaloid of tobacco Nicotiana tabacum) of the Solana-ceae. Anabasine is the main alkaloid of Anabasis aphylla (Chenopodiaceae), although trace amounts are also present in tobacco. Both nicotine and anabasine possess strong insecticidal activity. The structures of these alkaloids also have similarities in that one contains a pyrrolidine ring derived from ornithine and the other a piperidine ring derived from lysine, both of which are joined at C-3 of the pyridine ring, itself derived from nicotinic acid [1]. These alkaloids were described in detail in Chapters 3 and 4 on ornithine-and lysine-derived alkaloids, respectively. The procedure for the formation of nicotine and anabasine by condensation of A -pyrrolidine and A -piperidine with a nicotinic acid moiety is shown in the figure [2]. 

A number of other compounds with similar structures [e.g., ammodendrine (28) from Ammodendron conollyii, Fa-baceae] are not derived from nicotinic acid, but wholly from lysine derived units (Fig. 29.10) (Herbert, 1988). 

Common characteristics in the biosynthesis of these alkaloids, that they are elaborated from the lysine derived A -piperideine, coupling either to an aliphatic- (from acetyl-CoA precursor, e.g., pelletierine and co-alkaloids), or an aromatic part (from cinnamoyl-CoA precursor, e.g., pipeline and other amides lobeline, lobelanine and related alkaloids). 

The origins of the skeletal fragments of 6.19), 6.20), and 6.21) not accounted for by lysine (and A -piperideine) are as follows. The C3 side-chain in A -methylpelletierine 6.19) has its origins in acetate plausibly via acetoacetate [9]. The side-chain of sedamine 6.21), on the other hand, derives from phenylalanine, probably by way of its deamination product, cinnamic acid [10, 11]. Benzoylacetic acid, a normal in vivo transformation product of cinnamic acid, may also reasonably be included in the pathway to this alkaloid, as it is in, e.g., the biosynthesis of lobeline 6.34) and of phenanthroindolizidine alkaloids (see Section 6.2.2). The pyridine ring of anabasine 6.20) arises from nicotinic acid [14] by way presumably of 6.5) (cf nicotine. Section 6.2.2). The acid precursors (see Scheme 6.6) for 6.19), 6.20) and 6.21), have in common an electron-donating functionality (Scheme 6.7) which may react with A -piperideine 6.18), possibly with concommitant decarboxylation, to give the alkaloids (cf fatty acid biosynthesis. Section 1.1.2). 

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