Proline hydroxyl groups

The hydroxyl group is added to proline after synthesis into protein and is only found in collagen and gelatine — has two asymmetric carbon atoms... 

Table 7 includes many structurally unique nonprotein amino acids with heterocyclic units as part of the structure. These amino acids are isolated from various sources and exhibit interesting bioactivities. In most cases, enzymatic modification of proline occurs through installation of hydroxyl groups, halogenated side chains, and alkyl side chains to give rise to the observed structural diversity. 

Ascorbic acid or vitamin C is found in fruits, especially citrus fruits, and in fresh vegetables. Man is one of the few mammals unable to manufacture vitamin C in the liver. It is essential for the formation of collagen as it is a cofactor for the conversion of proline and lysine residues to hydroxyproline and hydroxylysine. It is also a cofactor for carnitine synthesis, for the conversion of folic acid to folinic acid and for the hydroxylation of dopamine to form norepinephrine. Being a lactone with two hydroxyl groups which can be oxidized to two keto groups forming dehydroascorbic acid, ascorbic acid is also an anti-oxidant. By reducing ferric iron to the ferrous state in the stomach, ascorbic acid promotes iron absorption. 

Azacyclols arising from amide-amide interaction have been extensively investigated. The p-nitrophenyl ester (60) of the linear tripeptide N-benzyloxycarbonyl-L-alanyl-L-phenylalanyl-L-proline undergoes a double cyclization when left in an aqueous buffer-dioxane (1 1) solution for 1 h, to produce cyclol (61) (7 ICC 1605). The hydroxyl group of the cyclol could be converted to the methyl ether by treatment with methyl iodide-silver oxide. The structure of the cyclol (61) could be confirmed by X-ray crystallography of the corresponding p-bromobenzyloxycarbonyl derivative (7 ICC 1607). 

Fragments of hydroxy-L-proline-rich protein obtained from the primary cell-walls of dicots invariably contain arabinosyl and galactosyl residues and a series of hydroxy-L-proline arabinosides mono-, di-, tri-, and tetra-arabinosides, glycosidically linked to the hydroxyl group of hydroxy-L-proline have been isolated from wall preparations obtained from suspension-cultured sycamore- and tomato-cells,228,230 and separated chromatographically on Chromobeads B.231 The hydroxy-L-proline tetraarabinoside is the preponderant molecular species obtained from the dicot primary cell-wall protein. Little or no nonglycosylated hydroxy-L-proline appears to be present.41,42,231 This wall protein is, therefore, clearly a glycoprotein. 

Hydroxyproline and hydroxylysine result from the hydroxylation by specific hydroxylases of proline and lysine residues after their incorporation into a-chains. The enzymes require ascorbic acid as a cofactor. [Note An ascorbic acid deficiency results in scurvy.] The hydroxyl group of the hydroxylysine residues of collagen may be enzymatically glycosy lated (most commonly, glucose and galactose are added sequentially to the triple helix). 

Glycans can be attached to the protein backbone via the amide nitrogen of asparagine (Asn) in the consensus sequence -Asn-X-Ser/Thr- (X is any amino acid except proline, A-glycosylation, Fig. 31 A) or the hydroxyl group most... 

The alio series of the pumiliotoxin A class have an additional hydroxyl group that has been placed at C-7 on the indolizidine ring, without assignment of configuration. Three members of the alio series have been assigned the tentative structures (7), (8), and (9).3 Pumiliotoxins A and B are relatively toxic, and comparable in potency to strychnine. Pumiliotoxin B has a potent cardiotonic and myotonic activity.3 An enantioselective total synthesis of pumiliotoxin A alkaloids from L-proline has already been announced.4... 

It is believed that proteins and tannins interact via hydrogen bonding and hydro-phobic effects. Hydrogen bonds can be formed between the hydroxyl groups of phenolic compounds and carbonyl and amide groups of proteins. Hydrophobic interaction can occur between the benzenic nuclei of phenolic compounds and the apolar side-chains of amino acids such as leucine, lysine, or proline in proteins. Several authors have observed the occurrence of hydrophobic interactions between proteins and tannins [16-20]. 

Schotten-Baumann type N-benzoylation was carried out on trans-4-hydroxy-L-proline 34,39 giving amide 43 in a satisfactory yield of 65%. The disappointing yield here could be attributed to difficulties experienced in recrystallization of the product 43. The amide 43 was esterified to give tert-butyl ester 44 using a modification of a procedure described by Widmer40 with dimethylformamide-dineopentyl acetal and tert-butanol as reagents. This provided crystalline 44 in 71% yield from 43 with no evidence of terf-butyl ether formation at the C-4 hydroxyl group (Scheme 12). 

To improve the aqueous solubility of 5 we also synthesized a cyclopeptide 6 containing hydroxyproline subunits [24]. Although this compound is very water-soluble, and in solution adopts a similar conformation to 5, it only forms 1 1 complexes with anions. A reason for the inability of 7 to form 2 1 complexes could be that the hydroxyproline subunits in 6 are better solvated than prolines in aqueous solution, and the desolvation required for aggregation of two cyclopeptide molecules thus occurs less readily. Steric hindrance of hydroxyl groups from different cydopeptide moieties in the a dimeric complex of 6 could, moreover, also make aggregation difficult. Although peptide 6 cannot form sandwich-type complexes, it proved to be valuable for a quantitative determination of the anion affinity of 5, the results of which are summarized in Table 2.2.3 [24],... 

There are 20 different amino acids used in the synthesis of proteins these amino acids are listed in Table 3.1, which also contains the two commonly used symbols for each amino acid. The three-letter symbols are easier to remember, but the single-letter symbols are often used in writing long sequences. In many proteins some of the amino acids are modified after incorporation into proteins e.g., in collagen, a hydroxyl group is added to each of several proline residues to yield hydroxyproline residues. With the exception of proline, the a-amino acids that are incorporated into proteins can be represented by the formula shown in Fig. 3-1. 

Oxy-proline, (C4H7(OH)N)—COOH, a-(Hydroxy Pyrrolidine) Carboxylic Acid. As its name indicates oxy-proline is an hydroxy derivative of proline. The position of the hydroxyl group in the pyrrolidine ring is not known. 

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