S-Hydroxylysine

S-Hydroxylysine 5-Hydroxyl Lactonizing agents 5-Lactone formation Not tested Ziirn, 1960... 

The preferential cleavage of peptide bonds next to S-hydroxylysine in collagen by the controlled action of acid in the cold has yet to be studied. 

When coUagen is synthesized, the amino adds proUne and lysine are incorporated into the chain of amino adds. These are later modified by two enzymes to form 4-hydroxyproline and S-hydroxylysine. Both of these enzymes require vitamin C to carry out these reactions. In fact, this is the major known physiological function of vitamin C. Without hydroxylation, hydrogen bonds cannot form and the triple hehx is weak, resulting in fragile blood vessels... 

Holm, B., Broddefalk, J., Flodcll, S., Wellner, E., and Kihlberg, J. (2000) An improbed synthesis of a galactosylated hydroxylysine building block and its use in solid-phase glycopeptide synthesis. Tetrahedron Lett. 56,1579-1586. 

Fig. 5. Schematic representation of the collagen IV molecule, which consists of two al(IV) chains and one a2(IV) chain. The non-triple-helical interruptions of the triple helix are indicated by black bars. The cysteine residues (C) and lysine or hydroxylysine (K) residues putatively involved in intra- or intermolecular bonds are shown. CHO designates a N-giycosidically bound oligosaccharide chain. The subscript numerals indicate the number of residues in a distinct region, summarized for all three a-chains. P designates a main pepsin cleavage site. In interruption 13, the a2(IV) chain forms a 21-residue-long loop, stabilized by an interchain disulfide bridge. NCI, Noncollagenous domain 1 TH, triple-helical domain 7 S, carboxyl-terminal domain.

Fig. 7. (A) A detailed model of the amino-terminal al(IV) and a2(IV) chains containing the 7 S domain and an adjacent segment of the main triple helix. The terminal sequence of both chains is nonhelical and contains lysines (K), hydroxylysines (K), and cysteines (C) that participate in intra- and intermolecular cross-linking. A helical cross-linking site is located about 30 nm from the amino terminus (N) of the molecule and contains cysteines and a hydroxylysine in the al(IV) chain involved in cross-linking plus a complex carbohydrate attachment site (CHO). The cap site within the main triple helix identifies a series of four triplets containing proline (P) and hydroxyproline (P), a composition that would be expected to form a very stable helical structure, [Data from Glanville et al. (1985) Siebold et al. (1987)]. (B) The antiparallel arrangement of type IV molecules with alignment of cross-linking sites.

III [ 1(IH)]3 Skin, muscle, arterial wall, uterus High hydroxyproline but low in hydroxylysine -S-S- bonds present... 

Leucine oxidized with "OH produces a 5 -hydroperoxy derivative which is subjected to chemical reduction to yield (2S)-y-hydroxyleucine, (2S,4S)-8-hydroxy-leucine, (2S,4R)-8-hydroxyleucine. The S -hydroxyleucines have been confirmed to be the reduction products of the corresponding hydroperoxyleucines. 5 -Hydro-xylysines are natural products formed by lysyl oxidase and therefore are not useful markers of radical-mediated oxidation. The other hydroxylysines are useful markers, however, with HPLC analysis of 9-fluorenylmethyl chloroformate (FMOC)... 

D24. Dunn, J. A., McCance, D. R., Thorpe, S. R., Lyons, T. J., and Baynes, J. W., Age-dependent accumulation of N epsilon-(carboxymethyl)lysine and N epsilon-(carboxymethyl)hydroxylysine in human skin collagen. Biochemistry 30, 1205-1210 (1991). 

M25. Morin, B., Bubb, W. A., Davies, M. J., Dean, R. T., and Fu, S., 3-Hydroxylysine, a potential marker for studying radical-induced protein oxidation. Chem. Res. Toxicol. 11, 1265-1273... 

Figure 3 Posttranslational modifications in collagen, (a) 3(S)-hydroxyproline. (b) 4(R)-hydroxyproline. (c) 5-hydroxylysine. (d) O-p-galactosyl-5-hydroxylysine. (e) 2-0-a-D-glucosyl-0-p-D-galactosyl-5-hydroxylysine.

During detailed characterization of a tryptic map of recombinant human tissue plasminogen activator (rtPA), a minor peak was resolved whose mass was not consistent with the expected set of tryptic peptides (L. Keyt and S.-L. Wu, unpublished observation). N-terminal sequence analysis of this fraction showed that it had a sequence containing residues 276-296 of rtPA with Lys-277 present as Hyl. We developed a modified amino acid analysis program capable of detecting hydroxylysine at levels down to 0.05 residues/mol to determine the distribution of Hyl in rtPA as well as in some other proteins derived from mammalian cells. 

Y. Kakimoto and S. Akazawa, Isolation and Identification ofNG, NG-Dimethylarginine, N-Epsilon-Mono-, Di-, and Trimethyllysine, and Glucosylgalactosyl- and Galactosyl-Delta-Hydroxylysine From Human Urine, Journal of Biological Chemistry 245 (1970) 5751 -5758. 

Other reagents are relatively specific for only one or several amino acids. These include the ninhydrin-bicarbonate reagent (P3) for phenylalanine and aspartic acid Ehrlich s reagent (S33) for tryptophan the nitrosonaphthol reagent (Al) for tyrosine the periodic acid reagent (S37) for serine, hydroxylysine, and ethanolamine the nitro-... 

The amino acid composition of collagen is distinctive. Glycine constitutes approximately one-third of the amino acid residues. Proline and 4-hydroxyproline may account for as much as 30% of a collagen molecule s amino acid composition. Small amounts of 3-hydroxyproline and 5-hydroxylysine also occur. (Specific proline and lysine residues in collagen s primary sequence are hydroxylated within the rough ER after the polypeptides have been synthesized. These reactions, which are discussed in Chapter 19, require the antioxidant ascorbic acid.)... 

Collagen s amino acid sequence primarily consists of large numbers of repeating triplets with the sequence of Gly—X—Y, in which X and Y are often proline and hydroxyproline. Hydroxylysine is also found in the Y position. Simple carbohydrate groups are often attached to the hydroxyl group of hydroxylysine... 

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