|
Proposal towards a Normalization of Pteridine Nomenclature Juan Ferre, Kenneth Bruce Jacobson1), and Wolfgang Pfleiderer1)Department of Genetics, Faculty of Biology, University of Valencia, E-46100 Burjassot (Valencia), Spain 1)
Biology
Division, Oak Ridge National Laboratory, Oak Ridge, Tennessee
37831, U.S.A. (published in Pteridines 1990;2:129) Introduction Publications, workshops, and symposia on pteridines have shown the lack of unified criteria to name and abbreviate this family of compounds. Since the pteridine field has grown very rapidly in the last decades, and it is foreseen that it will continue to do so, much confusion can be avoided if rules are adopted regarding nomenclature and use of abbreviations. Three years ago, the IUPAC-IUB Joint Commission of Biochemical Nomenclature published some recommendations in the nomenclature of folates (Eur.J.Biochem. 1987, 168: 251-253), which are summarized as follows: It was proposed that the compounds of the folic acid groups are based on pteroic acid, which is derived from the 4-(pteridin-6-ylmethyl)aminobenzoic acid skeleton. The salts and the acyl group deduced from the pteroic acid are named pteroates and pteroyl, respectively. The systematic name of pteroic acid is 4-{[(2-amino-3,4-dihydro-4-oxo-pteridine-6-yl)methyl]}amino benzoic acid. However, the use of ‘dihydro’ - in this systemic name of the parent non-reduced compound should be carefully distinguished from the use of ‘dihydro’ - in the names of reduced derivative, where it refers to the pyrazine ring. 2-Aminopteridin-4-(3H)-one also occurs in other biologically important derivatives, and may be called pterin. The atoms of pteroic acid are numbered as indicated in the formulae. It should be noted that the nitrogen atoms numbered 5, 8, and 10 are unambiguously defined. It is therefore unnecessary to introduce the locant N into names when indicating substitution on these atoms. The carbon atoms common to the two rings are numbered 4a, 8a, so as to permit description of compounds reduced at these positions. The compound in which pteroic acid is conjugated with one or more molecules of L-glutamate are named pteroylglutamate, pteroyldiglutamate, etc. It is assumed that the second and subsequent molecules of glutamate are each linked by amide bonds to the preceding molecule of glutamate through the d-carboxyl group of the latter. Folate and folic acid are the preferred synonyms for pteroylglutamate and pteroylglutamic acid, respectively. Reduced compounds are indicated by the prefixes ‘dihydro’-, ‘tetrahydro’-, etc., with numerals indicating the positions of the additional hydrogen atoms, if known. A tetrahydro-compound is assumed to be substituted in the 5, 6, 7, and 8 positions, and a dihydro-compound is assumed to be substituted in the 7 and 8 positions, unless otherwise indicated. As the absolute configuration of C-6 in the natural stereoisomers of the tetrahydropteroylglutamates is known, R, S, or ambo - should be used to designate the configuration whenever possible. (The prefix ambo - indicates that a mixture is present, one of those compounds is R and the S at the locus designated; it is especially useful when they are not present in equal proportions, because of the presence of other chiral centres in the molecule, such as those of glutamate residues.) All the known natural stereoisomers in the folate series have the same configuration as (6S)-tetrahydrofolate, with the H on C-6 placed below the plane of the paper when the formula is drawn as in the above picture, but are variously designated R or S according to the priority rules. Where the configuration at C-6 is unknown in compounds bearing a hydrogen atom at this point, the symbols (+), (-) or (+) may be used to indicate optical activity. Symbols and Abbreviations It is often convenient to designate compounds of this series by symbols for the sake of brevity, particularly in equations, tables, and figures. The following principles are to be applied. In all cases where confusion might arise, symbols are to be defined, or the names of compounds written out in full. a) Folate is preferred to folic acid, and, because it is short, it should not be abbreviated. b) Pteroate (or pteroyl or pteroic acid) is indicated by the three-letter symbol Pte. c) The pteroylglutamates and the corresponding acids are indicated by the symbols PteGlu, PteGlu3, etc., the subscript numerals indicating the number of the glutamate units. The symbol Glu is taken from the standard amino-acid symbols. d) Reduced derivatives are indicated by H2 or H4 in front of the main symbol with an indication of the position, if necessary, e.g. H2-folate, H4-PteGlu3. DH and TH should not be used. e) Substituents are indicated by symbols derived from their abbreviated formulae, prefixed by appropriate locants. e) H2, H4 and other prefixes may be used with ‘folates’ or with ‘pteroylglutamates’ when reduced or reduced-modified compounds are meant. The following are some examples of natural stereoisomers: (6S)-H4folate (6S)-5,6,7,8-tetrahydrofolate (6S)-5,6,7,8-tetrahydropteroylglutamate (6R)-5,10-CH2-H4folate (6R)-5,10-methylenetetrahydrofolate (6S)-5-CH3-H4PteGlu3 (6R)-5-methyltetrahydropteroyltriglutamate (6R)-5,10-CH+-H4folate (6R)-5,10-methenyltetrahydrofolate (6-ambo)-5-HCO-H4folate (6-ambo)-5-formyltetrahydrofolate. It is desirable that something similar could emerge for the simpler unconjugated pteridines according to some informal discussions initiated at the Snowbird meeting at Utah in 1988, and from later conversations with other scientists of the field at the pteridine congress at Zürich 1989. It should be noted that one of the goals of the following recommendation is to keep the number of trivial names to a minimum, and at the same time to explore all the advantages that their use can permit. Main Guidelines The basic nuclei of the naturally occurring pteridine derivatives are pterin (2-aminopteridin-4(3H)-one) and lumazine -(pteridine-2,4(1H, 3H)-dione). 1. On the oxidation state 1a. The oxidation state is considered as in the folates, i.e., a tetrahydro-compound is assumed to be substituted in the 5, 6, 7, and 8 positions, and a dihydro-compound in the 7 and 8 positions, unless otherwise indicated. 1b. A name not indicating the oxidation state should be taken as being the fully oxidized state. 1c. Similarly to the folate recommendations, the prefix indicating reduction should be placed before the name of the compound. Examples: H2biopterin = 7,8-dihydropterin 5,8-H2biopterin =5,8-dihydrobiopterin 2. One the trivial names 2a. Trivial names should be preferred to chemical names for natural pteridines. 2b. A trivial name should unequivocally define the side chain attached to the pterin nucleus. For example, neopterin should be used to designate the natural isomer, and L-neopterin should be used for L-erythro-neopterin. It would be incorrect to say L-threo-neopterin, since the name monapterin already exists for such a side chain configuration. Examples: Neopterin = 6-(D-erythro-1,2,3-trihydroxypropyl)-pterin Monapterin = 6-(L-threo-1,2,3-trihydroxypropyl)-pterin Biopterin = 6-(L-erythro-1,2-dihydroxypropyl)-pterin Biolumazine = 6-(L-erythro-1,2-dihydroxypropyl)-lumazine Ciliapterin = 6-(L-threo-1,2-dihydroxypropyl)-pterin Dictyopterin = 6-(D-threo-1,2-dihydroxypropyl)-pterin Bio- = (L-erythro-1,2-dihydroxypropyl)- Cilia- = (L-threo-1,2-dihydropropyl)- Neo- = (D-erythro-1,2,3-trihydroxypropyl)- Mona- = (L-threo-1,2,3-trihydroxypropyl)- 2c. Unless otherwise specified, the trivial name will refer to a side chain in the 6-position of the pterin ring. To be consistent with recommendation 2b, for the same side chain, the same trivial name should be used, even when the substitution takes place in another position different to C-6. Therefore, we suggest: 7-biopterin instead of primapterin for the 7 isomer of biopterin; 7-neopterin instead of anapterin for the 7 isomer of neopterin; 7-xanthopterin instead of isoxanthopterin. 3. On the abbreviations
3a. A 3-letter abbreviation code is desirable for the sake of brevity, particularly in some cases (e.g. equations, tables, and figures). 3b. Whenever possible, the abbreviation will consist of the two first letters of the name, followed by a “p” standing for pterin, or a “l” standing for lumazine. 3c. Prefixes as iso-, neo-, auro-, etc. should be placed abbreviated in italics in front of the main symbol. 3d. Reduced derivatives will be indicated by H2 of H4 in front of the main symbol. 3e. A number on the left of the main symbol will indicate the position of the substitution (if different than the 6-position). Examples: Bip = biopterin Bil = biolumazine 7-Bip = 7-biopterin H2Bip = H2biopterin Nep = neopterin Nel = neolumazine H2Nep-P3 = H2neopterin triphosphate Mop = monapterin Mep = methanopterin Tap = tatiopterin Sap = sarcinapterin Sep = sepiapterin (H2Lap) Sel = sepialumazine Lap = lactoylpterin Drp = drosopterin n-Drp = neodrosopterin i-Drp = isodrosopterin a-Drp = aurodrosopterin Xap = xanthopterin Xal = xantholumazine (violapterin) 7-Xap = 7-xanthopterin (isoxanthopterin) Chp = chrysopterin (7-CH3-xap) H2Ahp = H2acetylhomopterin Pyp = pyruvoylpterin (Pyr is sometimes used for pyruvic acid) Prp = propionylpterin H2Prp = 2’-desoxysepiapterin (formerly isosepiapterin) Ptr
= pterin
(Pte cannot be used since it has been adopted by folate
researchers to Ekp = ekapterin Erp = erythropterin Eup = euglenapterin Hmp = hydoxymethylpterin Lcp = leucopterin Lpp = lepidopterin Lum = lumazine Ril = ribolumazine Pul = putidolumazine Leu = leucettidine Justification: A 3-letter code abbreviations allows a clearer description than a 1-letter code. 4. Other recommendations Some trivial names that have long been used in the literature, for different reasons are now found to be inappropriate or confusing. For this reason, we propose to substitute them with the following alternative names: Old name: Prosposed name: sepiapterina H2lactoylpterin isosepiapterina H2propionylpterin 2’deoxysepiaterina H2propionylpterin pyrimidodiazepine (PDA) b H2acetylhomopterin bufochromec neopterin violapterind 7-xantholumazine sepialumazinea H2lactoyllumazine luciopterind 8-methyl-7-xantholumazine a The confusion comes from the oxidation state. b It has been used as the abbreviation of 2-amino-4-oxo-6-acetyl-7,8-dihydro-3H,9H-pyrimido [4,5,6]-[1,4] diazepine (the precursor of drosopterins). c It was proved that it is neopterin and that the former structure (the L-isomer) was wrong (Fukushima and Akino, 1986, Arch. Biochem. Biophys. 128: 1-5). d It is not a pterin, but a lumazine. Conclusion These abbreviations are proposed to allow clear, unambiguous designation of the pteridines. We recommend their use in all reports and publications and urge the established pteridine investigators to adopt them to help implement their widespread utilization. We recognize that the redefinition of the oxidation state of sepiapterin will be a stumbling block but suggest that the overall benefit of a uniform nomenclature is sufficient justification to overcome difficulties associated with such a redefinition of a single member.
|