Hydroxylation side chain

Figure 13.1 Degradation of glucosinolates. Hydrolysis is catalyzed by myrosinases and gives rise to different degradation products dependent on the structure of the glucosinolate side chain and the hydrolysis conditions. (I) isothiocyanates, the major product at pH >7 (II) nitriles, the major product at pH <4 (ID) thiocyanates, produced from 2-propenyl-, benzyl-, and 4-methylthiobutylglucosinolates (IV) oxazolidine-2-thiones, produced from glucosinolates with P-hydroxylated side chains, (V) epithionitriles, produced in the presence of epithiospecifier proteins.

The second family of secreted proteins that is covalently lipidated is the family of Wnt proteins. They are also involved in numerous processes like proliferation of stem cells, specification of the neural crest, and the expanding of specific cell types. The correct regulation of this pathway is important for animal development. Willert and coworkers were the first to isolate an active Wnt molecule. Mass spectroscopy studies carried out with the isolated protein revealed that cysteine 93 is palmitoylated. Mutating this amino acid to alanine led to almost complete loss of the signaling activity. Later in 2006, a second lipidation was found on a serine in Wnt3a. " In this case, the hydroxyl side chain is acylated with palmitoleic acid. This unsaturated fatty acid seems to be crucial for the progression of the protein through the secretory pathway. The attachment of two different lipid chains may therefore serve different functions. ... 

Serine (Ser or S) ((S)-2-amino-3-hydroxypropanoic acid) is a polar, neutral, uncharged amino acid with the formula H00CCH(NH2)CH20H. It has an aliphatic hydroxyl side chain and can be seen as a hydroxylated version of Ala. Ser participates in the biosynthesis of purines and pyrimidines and is also the precursor to several amino acids including Gly, Cys, and Trp (in bacteria). In addition, it is the precursor to numerous other metabolites, including sphingolipids and is present in enzymes such as a-chymotrypsin. Ser, Asn, and aspartate disrupt a helices. 

Threonine (Thr or T) ((2S,31( )-2-amino-3-hydroxybutanoic acid) has an aliphatic hydroxyl side chain and is classified as a polar, uncharged amino acid with the formula HOOCCH(NH2)CHOHCH3. Together with Ser and Tyr, Thr is one of the three proteinogenic amino acids bearing an alcohol group. Thr can be seen as a hydroxylated version of Val. With two chiral centers, Thr can exist in four possible stereoisomers, or two possible diastereomers of L-Thr. However, the name L-Thr is used for one single enantiomer, (2S, 3if)-2-amino-3-hydroxybutanoic acid. The second diastereomer (2S,3S), which is rarely present in nature, is called L- //o-Thr. 

Figure 6 shows the proposed subunit assembly structure of the nicotinic acetylcholine receptor channel." The inner wall of the lower half part is surrounded by hydroxyl side chains from Ser and Thr, and by carboxylates or amides from Asp, Glu, and Gin at the mouth. Furthermore, a Lys residue seems to offer ion pairing with the carboxylate at the mouth. Considering the possibly similar stabilizing effect of ether and hydroxyl groups to cations, the proposed artificial supramolecular channel could be regarded as a good model of the acetylcholine receptor channel, which selects cations over anions, but does not discriminate between alkali metals. 

The 2-(oMo-polyhydroxyalkyl) benzimidazoles are weak bases derived from o-phenylenediamine by condensation with an aldonic or closely related hydroxy acid. The present review includes substances of this type containing hydroxylated side chains of one to seven carbon atoms in length. Typical is the benzimidazole from D-glucose via D-gluconic acid. The side chain is attached at position 2 of the benzimidazole nucleus,... 

What is now known as C-alkaloid A was first isolated by King (14) from S. toxifera bark and named toxiferine IV when it was again isolated from a calabash (16), its identity (15) with King s alkaloid was not known, and the second name has become established. C-Alkaloid A, picrate, mp 228°-229°, [a]D +64° (chloride in water), is formed from toxiferine I under the same conditions that produce C-calebassine from C-dihydrotoxiferine I. These include aerial oxidation in a mixture of pyridine, water, and isobutyric acid (127) or pivalic acid (114) when the acid used is acetic acid, C-alkaloid A is produced along with its 0,0-diacetyl derivative (114) as described earlier in the case of toxiferine I. Most of the properties of C-alkaloid A and its UV-spectrum in neutral, alkaline, and strongly acidic solution are identical with those of C-calebassine. Also, its NMR-spectrum corresponds with that of C-calebassine, with the exception of those signals owing to the hydroxylated side chains. C-Alkaloid A therefore has structure CXXIII (Ri = R2 = OH) C-alkaloid F (see Section III, F) is CXXIII (Ri = H, R2 = OH). 

This protein has been studied in detail by the LIS method [113,114]. The protein binds two equivalents of Ca2+ in two distinct binding domains known as CD and EF hands. Each of the domains consists of a short a-helical structure, a loop around the Ca2+ site which contains regularly spaced carboxyl, carbonyl, and hydroxyl side-chain ligands for the metal ion, followed by a second a-helical region. The binding domains have a very high affinity... 

The asymmetric total synthesis of prostaglandin Ei utilizing a two-component coupling process was achieved in the laboratory of B.W. Spur. The hydroxylated side-chain of the target was prepared via the catalytic asymmetric reduction of a y-iodo vinyl ketone with catecholborane in the presence of Corey s CBS catalyst. The reduction proceeded in 95% yield and >96% ee. The best results were obtained at low temperature and with the use of the B-n-butyl catalyst. The 6-methyl catalyst afforded lower enantiomeric excess and at higher temperatures the ee dropped due to competing non-catalyzed reduction. 

The differences in binding orders between TBPA and TBG suggest that different structural features may play a key role in receptor interactions. It has been shown (4,28) that TBG also preferentially binds to a tetraiodo-4 -phenoxide ion, but since Ti is the strongest binder, this suggests a different side chain stereochemistry. Here we can assume that it is the twist-skewed diphenyl ether conformation which orients the Tside chain for optimal receptor-hormone interactions. In the case of the nuclear proteins optimal binding is observed for a distally oriented 3 -I and a 4 -hydroxyl. Side chain requirements appear to be similar to those of TBG (28,31). 

Phosphoproteins.— Details of the amino-acid sequences at the phosphorylation sites of two proteins involved in glycogen metabolism have been published, and they show unusual features. For example, there is an unusually high proportion of hydroxyl side-chains near the phosphoserine at one of the phosphorylation sites in glycogen synthetase, ... 

The oligosaccharide is involved at its reducing end in a glycosidic bond with one of the hydroxylated side chain residues of the polypeptide. They are the ones derived from L-serine 13.11, L-threonine 13.12, L-hydroxylysine 13.13, and... 

The reversible phosphorylation of proteins is one of the most widespread posttranslational modifications, mediating responses to internal and external signals in a variety of cellular processes [1-3]. In eukaryotes 30-70 % of all proteins are phosphorylated on tyrosine (Tyr), threonine (Thr), and/or serine (Ser) residues [4-6]. Protein phosphorylation is catalyzed by protein kinases, which transfer the y-phosphate of ATP to a hydroxyl side chain, resulting in the formation of a phosphate monoester. Protein phosphatases hydrolyze these phosphate monoesters and make protein phosphorylation a reversible modification [4]. 

---