Pteridine ring

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

Figure 2. Asp27 interaction with the pteridine ring of dihydrofolate (R = PBH-GXO).

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... 

The free energy associated with the hydride ion transfer from C4 of the nicotinamide ring to C6 of the pteridine ring was computed in a manner... 

We do not want to consider the chemistty of the pteridine ring system here, but instead we... 

Natnral folate, introduced through the diet, are mostly reduced folates, i.e., derivatives of tetra-hydrofolate (THE), such as 5-methyl-THF (5-MTHF), 5-formyl-THF, and 5,10-methylene-THF, and exist mainly as pteroylpolyglntamates, with np to nine additional glutamate molecules attached to the pteridine ring. 

The investigations on the pyrido[2,3-6]pyrazine ring were inspired by the related pteridine ring, of importance in natural products. Pteridines are very reactive systems with both liquid ammonia and KNH2 in liquid ammonia, but in neither medium have anionic (j-adducts ever been detected. Such adducts presumably form initially and rapidly evolve toward covalent amination and ring contraction products.119,121... 

Pterin coenzymes such as folic acid (pteroylglutamic acid) and biopterin, which contain a dicyclic pteridine ring, a part of the skeleton of flavins, are also known to play versatile roles in biological redox reactions [67]. The oxidizing ability of the excited state of a pteridine derivative (lumazine [Lu])... 

Methylation of dUMP to give thymidylate is catalyzed by thymidylate synthase and utilizes 5,10-methylenetetra-hydrofolate as the source of the methyl group. This reaction is unique in the metabolism of folate derivatives because the folate derivative acts both as a donor of the one-carbon group and as its reductant, using the reduced pteridine ring as the source of reducing potential. Consequently, in this reaction, unlike any other in folate metabolism, dihydrofolate is a product (fig. 23.16). Since folate derivatives are present in cells at very low concentrations, continued syn-... 

If the type of the molecular frame A and the nature of the polaro-graphically active group R are known, it is possible to distinguish by means of a linear free energy relationship, the kind of the substituent X in the molecule R — A — X. From the measured value of the shift of the half-wave potential and by means of the tabulated values of the substituent constants, the substituent involved can be distinguished or some few substituents that are likely to be responsible for the observed shift of the half-wave potential can be sorted out. This type of application has been demonstrated (160) in the identification of the nature of the substituent and the determination of its position on a pteridine ring. 

The pteridine ring system is composed of fused pyrazine and pyrimidine rings, either of which might be attacked by a complex metal hydride. The reaction of pteridine (145), 2,4-dichloropteridine (146), or 2,4-dimethoxypteridine (147) with lithium aluminum hydride was reported to occur with reduction of the pyrazine ring to give the 5,6,7,8-tetrahydropteridine (148-150, respectively).150... 

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. 

---