Pteridine ring, structure

Folic acid is a conjugated molecule consisting of a pteridine ring structure linked to para-aminobenzoic acid (PABA) that forms pteroic acid. 

Structure of folic acid showing its components. The numbered part participates in one-carbon transfer reactions. In nature, folate occurs largely as polyglutamyl derivatives in which the glutamate residues are attached by isopeptide linkages via the y-carboxyl group. The pteridine ring structure is also present in tetrahydrobiopterin, a coenzyme in the hydroxylation of phenylalanine, tyrosine, and tryptophan (Chapter 17). 

Ion-pair HPLC (IP-HPLC) and reversed-phase HPLC (RP-HPLQ have been used to determine folate (Wilson and Horne 1984, 1986), most commonly in conjugation with fluorescence, ultraviolet and UV-visible (UV-vis) spectrometry (Vahteiisto et al. 1996) or electrochemical detection (BCD) systems (Kohashi et al. 1986 Lucock et al. 1989). The pteridine ring structure of the folate can be determined on the basis of its retention time determined by HPLC and spectral characteristics via the diode array detection (DAD) system (Selhub 1989). 

Figure 1. Tautomeric equilibrium of the pteridine ring and the structure of 7,8-dihydrofolate.

Changes in the pteridine ring affect the contacts between DHFR and the p-aminobenzoic acid (PBH) moiety. PBH maintains van der Waals contact with Phe31 in all four structures (1, 3, 5 and 6) with contact distances ranging within 0.4 A of one another. Contact is also observed with Leu54 in all four structures with distances ranging from 3.0 A to 2.8 A. Only in... 

Oxo-groups located at other positions on the pteridine ring were shown by Albert and Matsuura152 to affect the structure of the dihydropteridine formed. Thus, pteridin-4- and 6-ones and 2,6- and 4,6-diones were converted to the corresponding 7,8-dihydro-derivatives (153), whereas pteridin-7-one and 4,7-dione formed the corresponding 5,6-dihydro-derivatives (154) on reaction with potassium borohydride. 

More information about the mechanism of the Viscontini reaction has been collected from model studies condensing 4,5,6-triamino-2-methylthiopyrimidine (338) in a similar manner with the phenylhydrazones of l- (339) and D-arabinose and omitting the iodine oxidation step (Scheme 55). Under these conditions an interesting intermediate, consisting of a tricyclic pteridine ring system (341), was formed by intramolecular adduct formation of the trihydroxypropyl sidechain on to the 7-position of the 5,6-hydropteridine precursor (340) (Scheme 55). The main reaction product could be crystallized and the structure unambiguously proven by an x-ray analysis <90HCA808). 

A closer look at these events reveals that bacteria synthesize folic acid using several enzymes, including one called dihydropteroate synthetase, which catalyzes the attachment of p-aminobenzoic acid to a pteridine ring system. When sulfanilamide is present it competes with the p-amino-benzoic acid (note the structural similarity) for the active site on the enzyme. This activity makes it a competitive inhibitor. Once this site is occupied on the enzyme, folic acid synthesis stops and bacterial growth stops. Folic acid can also be synthesized in the laboratory. ... 

Kuyper et al. (208) modeled the binding of the bacterial DHFR-selective antibiotic trimethoprim (11 A) using the X-ray structure of the . coli-methotrexate complex. They assumed that the pyrimidine ring of trimethoprim would bind analogously to the corresponding pteridine ring of methotrexate (their model was later shown to be qualitatively correct by... 

The crystal structure of the E. colt DHFR/MTX binary complex (9) reveals that the inhibitor binds in the active site in a kinked fashion (Figure 8). Asp-27 forms a salt-bridge to the bound pteridine ring while Phe-31 allows for the bend in the bound inhibitor. The remainder of the active site cavity surrounding the pterin ring is composed of amino acid residues that create a very hydrophobic environment. 

Plants use NADH. Fungi and bacteria use NADPH. The molybdenum is bound to a cofactor containing a pteridine ring to form molybdopterin (see here). All molybdenum-requiring enzymes except nitrogenase contain a structure similar to molydopterin. 

Folates exist in many chemical forms. The coenzyme form that functions in accepting one-carbon groups is tetrahydrofolate polyglutamate (Fig. 40.2), generally just referred to as tetrahydrofolate or FH4. It has three major structural components, a bicyclic pteridine ring, para-aminobenzoic acid, and a polyglutamate tail consisting... 

The conversion of serine to glycine involves the transfer of a one-carbon unit from serine to an acceptor. This reaction is catalyzed by senne hydroxymethylase, with pyridoxal phosphate as a coenzyme. The acceptor in this reaction is tetra-hydrofolate, a derivative of folic acid and a frequently encountered carrier of one-carbon units in metabolic pathways. Its structure has three parts a substituted pteridine ring, /(-aminobenzoic acid, and glutamic acid (Figure 23.11). Folic acid is a vitamin that has been identified as essential in preventing birth defects consequently, it is now a recommended supplement for all women of... 

FIGURE 5.5 Structures of methotrexate (a) and the WABE variants most similar (b) and most dissimilar (c) by circular fingerprints when there are three WABE changes. Structure (c) appears very different because circular fingerprints are particularly sensitive to changes in linkers (C —> N) and rings (N —> N+ in the pteridine ring). For color details, please see color plate section. 

Fig. 22.3 a Structure formula of folic acid, b Schematic representation of self-assembled columnar stacking of pterin (or pteridine)-rings in folic acid... 

For a long time before the ring structure of pterins was known, compounds containing the pteridine ring were being prepared. In 1895, 2,4-dihydroxy-pteridine was prepared by oxidation of tolualloxazine and decarboxylation of the resulting 2,4-dihydroxypteridine-6,7-dicarboxylic acid, and the same compound was prepared in 1907 by the action of hypobromite on pyrazine-2,3-dicarboxamide. The condensation of 4,5-diaminopyrimidine and benziF to form 6,7-diphenylpteridine reported in 1906 was the first example of the most versatile general method of pteridine synthesis. 

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