Amino acids adduct formation

Scheme 42. Reassignment of ellipticine quinone amino acid adduct 258 and proposed mechanism of formation by Potier and co-workers (107).

When sulfur atoms are introduced into the amino acids, the formation of silver-sulfur bonds appears to be of critical importance. The involvement of the other two donor centres, i.e. NH2 and CO2, however, then becomes less clear. It was discovered that reaction of silver nitrate with either Cu or salts of 5-methyl-L-cysteine gave rise to adducts, where the silver... 

S-phase blockage of the cell cycle. They also speculated that DNA-protein cross-links are likely to be responsible for disruption of DNA interactions with transcription factors, but the formation of DNA-amino acid (or GSH) adducts can play a protective role by preventing the involvement of Cr(III) in more damaging DNA-DNA or DNA-protein lesions (181, 258). The latter suggestion contradicts the results of Zhitkovich and co-workers (251, 256) on the mutagenicity of DNA-Cr -amino acid adducts. 

Copper-promoted autoxidation of D-finctose-amino acids may be accompanied by the Strecker-like degradation pathway, which starts with decarboxylation of tire D-araZ)mo-hexos-2-ulose-amino acid adduct 64 and results in formation of the respective Strecker aldehydes. ... 

These reactions which lead to homocysteine formation in some creatures and its utilization in others are undoubtedly representative of a general thiol group transfer mechanism. The initial condensation of the donor thiol, most commonly cysteine, with some suitably reactive receptor generates a thioether. The differences in the requirement for O-acylation when starting from serine and homoserine may refiect two completely different mechanisms for this thiol substitution reaction. In the case of serine, the removal of the hydroxyl as hydroxide and the stabilization of an electrophilic centre on the side-chain carbon can be achieved through the pyridoxal phosphate-amino acid adduct. A similar example is in the carbon-carbon condensation between serine and imidazole in tryptophan... 

However, in the presence of oxygen, covalently bound amino acid-fatty acid adduct formation is significantly suppressed instead, the oxidized fatty acids listed in Table 3.35 are formed. 

Kataoka H., Miyake M., Saito K., Mitani K. Formation of heterocyclic amine-amino acid adducts by heating in a model system. Food Chemistry, 130 725-729 (2012). 

Usually, a rapid binding step of the inhibitor I to the enzyme E leads to the formation of the initial noncovalent enzyme-inhibitor complex E-I. This is usually followed by a rate determining catalytic step, leading to the formation of a highly reactive species [E—I ]. This species can either undergo reaction with an active site amino acid residue of the enzyme to form the covalent enzyme-inhibitor adduct E—I", or be released into the medium to form product P and free active enzyme E. 

Tin(Il) shows considerable affinity towards nitrogen, therefore is expected to activate the imino group. The diastereoselective addition of tin(II) enolates derived from thioesters 1 to x-imino-esters 2 is reported12. This reaction proceeds smoothly to afford. vi w-/j-amino acid derivatives 3 (d.r. 95 5) in good yields. Lithium, magnesium, and zinc enolates do not react while titanium enolates give the adducts in low yield with preferential formation of the anti-isomer. 

Other cyclizations at phosphorus have been observed when certain phosphinates were used in the acid-catalyzed Mannich reaction. As observed previously with various phosphonous acid derivatives, reaction of aliphatic phosphinic acids with primary amines favored the formation of 2 1 adducts (73). Thus, glycine and other a-amino acids reacted under the typical conditions with excess formaldehyde and alkyl phosphonous acids to give the bis-phosphinylmethyl adducts 125. 

Formaldehyde fixes proteins in tissue by reacting with basic amino acids— such as lysine,5 7—to form methylol adducts. These adducts can form crosslinks through Schiff base formation. Both intra- and intermolecular cross-links are formed,8 which may destroy enzymatic activity and often immunoreactiv-ity. These formaldehyde-induced modifications reduce protein extraction efficiency and may also lead to the misidentification of proteins during proteomic analysis. 

Although this pathway involves the formation of an AMP adduct similar to the amino acid conjugation pathway, it is really not a conjugation pathway because the result is simply the inversion of configuration. 

Allenic amino acids belong to the classical suicide substrates for the irreversible mechanism-based inhibition of enzymes [5], Among the different types of allenic substrates used for enzyme inhibition [128, 129], the deactivation of vitamin B6 (pyr-idoxal phosphate)-dependent decarboxylases by a-allenic a-amino acids plays an important role (Scheme 18.45). In analogy with the corresponding activity of other /3,y-unsaturated amino acids [102,130], it is assumed that the allenic amino acid 139 reacts with the decarboxylase 138 to furnish the imine 140, which is transformed into a Michael acceptor of type 141 by decarboxylation or deprotonation. Subsequent attack of a suitable nucleophilic group of the active site then leads to inhibition of the decarboxylase by irreversible formation of the adduct 142 [131,132]. 

Y. Ueyama, Y. Monden, X. B. He, C. X. Lin, M. A. Momen, S. Mimura and A. Umemoto, Effects of bile acids on 2-amino-1-methyl-6-phenylimidazo-[4,5-b]pyridine-induced aberrant crypt foci and DNA adduct formation in the rat colon, J. Exp. Clin. Cancer Res., 2002, 21, 577. 

By employing A-acetamidoacrylates, rhodium-catalyzed 1,4-addition reactions can be applied to the enantioselective synthesis of a-amino acids. Unlike other typical 1,4-addition reactions, which install a stereogenic center at the p-position of the 1,4-adducts, this process deals with the formation of a stereocenter at the a-position, and thus the protonation (hydrolysis) step becomes an important step... 

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