:
Continued from Appendix
Contents of Addenda
1 Amide derivatives of amino acids and peptides
2 Selenium in peptides
3 Use of seco- in partially hydrolysed peptides
4 Structure formed by elimination of water between a β-carboxyl group and an α-NH group
5 Symbolism for Di-substituted Amino-Acid Residues
References for Addenda
Since publication of the recommendations on Nomenclature and Symbolism for Amino Acids and Peptides [31] a number of extensions have been published in the JCBN/NC-IUB Newsletter. These are listed below and cross references to them are incorporated into the main document on Amino Acids and Peptides in this World Wide Web version.
Addendum 1. Amide derivatives of amino acids and peptides
From the JCBN/NC-IUB Newsletter 1985 [33]
A hyphen on the left of a three-letter symbol represents (See 3AA-16.1) removal of H from N-2 of the amino acid, and a hyphen on the right of the symbol represents removal of OH from C-l, Ac-Gly-OMe represents CH3-CO-NH-CH2-CO-OCH3, for example. Tables in section 3AA-18.1 of these recommendations give many examples of such usage, but these tables do not include examples of amides of amino acids and peptides. As such amides are often used as substrates for peptidases, symbols for them are given here as examples of the symbolism.
Gly-NH2
glycine amide
Tos-Gly-NH-Ph
N-tosylglycine anilide
PhCO-Arg-NH-Np
benzoylarginine 4-nitroanilide (Np symbolizes the
4-nitrophenyl group as in Val-ONp for valine 4-nitrophenyl ester)
Cbz-Arg-NH-Nap
benzyloxycarbonyl arginine β-naphthylamide (where the symbol Nap refers to the 2-naphthyl group)
Ac-Ala-Ala-Pro-Val-NH-Mec
7-(acetyl-alanyl-alanyl-prolyl-valyl-amido)-4-methylcoumarin (Mec is often used to represent the 4-methylcoumarin-7-yl group. The release of 7-amino-4-methylcoumarin by peptidases, like that of 7-hydroxy-4-methylcoumarin, i.e. 4-methylumbelliferone, by glycosidases may be followed by fluorescence measurements.
It is largely a matter of personal preference how many single bonds are explicitly indicated, e.g. -O-Np or -ONp, -NH-Mec or -NHMec, compare -NH-Me or -NHMe, Ph-CO- or PhCO-. Readers may like to compare the symbols listed above with the symbol Tos-Phe-CH2Cl, constructed similarly for tosylphenylalanylchloromethane, the chloromethyl ketone discussed in sections 3AA-10.2 and 3AA-18.2.
Addendum 2. Selenium in peptides
From the JCBN/NC-IUB Newsletter 1986 [34] however see JCBN/NC-IUB Newsletter 1999 [38] for further recommendations on selenocysteine
As selenium-containing peptides are studied, the need for agreed names and symbols for selenium-containing amino acids and peptides is increasing.
Names. We recommend the name 'selenocysteine' for cysteine in which sulfur is replaced by selenium. One of the two meanings of the prefix thio- is replacement of oxygen by sulfur (section C-502 [14]), and seleno can similarly mean replacement of oxygen by selenium (section C-701.1 [14]). It seems reasonable to extent its usage to cover replacement of sulfur, so that the amino acid may be named 'selenocysteine', as opposed to the alternatives 'selenoserine' and 'hydroselenoalanine', which would adhere more strictly to the existing rules of organic nomenclature but would be likely to be more obscure in practice. [The name hydroseleno for the HSe-group (section C-701 [14]) uses the term seleno in different sense from that cited above.] The name selenocysteine has the advantages that (i) it is already widely used; (ii) cysteine is the biological precursor of selenocysteine; and (iii) selenocysteine is closer in properties to cysteine than to serine or alanine.
By extension, the prefix seleno may be applied to trivially named peptides such as glutathione to represent replacement of sulfur by selenium.
Symbols. We note that Günzler et al. [35] have used Sec and X as the three- and one-letter codes respectively, with appropnate definitions in the paper. This practice seems a useful addition to the existing symbols [31], though we would recommend that authors take care to emphasize that this use of X is more specific than the existing use of X to represent an unknown or 'other' amino acid [31]. We thank Dr Günzler for bringing it to our attention.
Addendum 3. Use of seco- in partially hydrolysed peptides
From the JCBN/NC-IUB Newsletter 1986 [34]
De Haën et al. [36] have used the prefix [seco-m/n]
attached to the name of a peptide to indicate the derivative obtained by hydrolysis of the
bond between residues m and n of the peptide. This usage, for which they
thank R. Schwyzer, seems to be a helpful extension to recommendations for describing
modifications of named peptides [31], and it may be illustrated by the
following examples :
The suggested use of the prefix seco- for peptides is slightly different from its use for other compounds. The bond cleaved in a peptide is replaced by OH and H; the bond cleaved in other compounds is replaced by two H atoms (section F-4.7 [14]). The second formula above contains the symbols -Phe-OH and H-Gln- for C- and N-terminal residues to emphasize that they are unsubstituted (section 3AA-17.6 [31]), but they could equally correctly be represented as -Phe and Gln-. Similar emphasis is used in the fourth formula. The need for a similar symbol to indicate hydrolysis that brings about ring opening rather than creation of two molecules may also exist for homodetic cyclic peptides, i.e. peptides such as gramicidin S in which the ring consists solely of amino-acid residues in eupeptide linkage. However, no system for dealing with these cases has been established, and we would caution biochemists that simple application of the prefix seco- as in heterodetic cyclic peptides such as oxytocin is inappropriate because there is no tetminus in a homodetic cyclic peptide and hence no unambiguous way of numbering residues.
Addendum 4. Structure formed by elimination of water between a β-carboxyl group and an α-NH group
From the JCBN/NC-IUB Newsletter 1989 [37]
Many systems of terminology have been and continue to be used to represent the type of
structure formed by elimination of water between the β-carboxyl group of an aspartate
residue and the α-NH group of the next residue in a peptide or polypeptide. The
general question of the naming of cyclic peptides is the subject of a current project of
JCBN. For the immediate case considered here, JCBN believe that the existing recommendations imply that the proper three-letter symhol for the structure is 
in which the vertical line above the ordinary three-letter symbol for aspartate indicates
participation of the β-carboxyl (Sections 3AA-16.4,
3AA-16.5 of [31]). Of the possible
names that have been suggested, 'anhydroaspartic residue' seems to be the clearest concise
way of indicating the type of structure. We thank Dr A. Zagari for bringing this point to
our attention.
Addendum 5. Symbolism for Di-substituted Amino-Acid Residues
From the JCBN/NC-IUBMB Newsletter 2009 [38]
It is recommended that a comma be used between the symbols for two different substituents on the same functional group, in particular, on the N-terminal amino group of a peptide, e.g., Bn,Me-Trp-Gly-... Similarly, two substituents on a side-chain amino group are indicated within parentheses and are separated by a comma, e.g. ...-Lys(Ac,Me)-Ser-... Identical substituents are indicated by a subscript index, as usual, e.g. Me2-Lys-... However, care should be taken when specifying substituents on the nitrogen atom of a peptide bond within a peptide chain. It is recommended that such a substituent be placed within parentheses on the left-hand side of the amino-acid symbol, e.g. Lys-(Me)Ala-... Note that the position of the hyphen indicates the position of the methyl group, i.e. that it is attached to the amino group of the alanyl residue, whereas Lys(Me)-Ala-... indicates that the methyl group is attached to N6 of the lysyl residue.
Note: Lys-Me-Ala, which is analogous to the form used for substituents on the N-terminal amino group, is not an alternative option because it places the methyl group between the two amino-acid residues.
14. International Union of Pure and Applied Chemistry (1979) Nomenclature of Organic Chemistry, Sections A, B, C, D, E, F and H, Pergamon Press, Oxford.
31. IUPAC-IUB Joint Commission on Biochemical Nomenclature (JCBN), Nomenclature and symbolism for amino acids and peptides. Recommendations 1983, Biochem. J. 219, 345-373 (1984); Eur. J. Biochem. 138, 9-37 (1984); 152, 1 (1985); Internat. J. Pept. Prot. Res. 24, following p 84 (1984); J. Biol. Chem. 260, 14-42 (1985); Pure Appl. Chem. 56, 595-624 (1984); Amino Acids and Peptides 16, 387-410 (1985); also pp. 39-69 in [32].
32. International Union of Biochemistry (1992) Biochemical Nomenclature and Related Documents, 2nd edition, Portland Press, pp 39-67.
33. IUPAC-IUB Joint Commission on Biochemical Nomenclature (JCBN), and Nomenclature Commission of IUB (NC-IUB). Newsletter 1985, Arch. Biochem. Biophys. 238, 688-692 (1985); Biochem. Internat. 10, following p 128 (1985); Biochem. J. 225, I-IV (1985); Biol. Chem. Hoppe-Seyler 366, 3-7 (1985); Biosci. Rep. 5, 185-188 (1985); Chem. Internat., 7-9 (1984(7)); Eur. J. Biochem. 146, 237-239 (1985); Trends Biochem. Sci. 9 (1984); 10 (1985), various issues.
34. IUPAC-IUB Joint Commission on Biochemical Nomenclature (JCBN), and Nomenclature Commission of IUB (NC-IUB). Newsletter 1986, Arch. Biochem. Biophys. 244, 393-395 (1986); Biochem. Internat. 12, following p 180 (1986); Biochem. J. 233, I-III (1986); Biol. Chem. Hoppe-Seyler 367, 1-4 (1986); Biosci. Rep. 6, 121-125 (1986); Chem. Internat. 8(4), 30-31 (1986); Eur. J. Biochem. 154, 485-487 (1986).
35. Günzler, W. A., Steffens, G. J., Grossmann, A., Kim, S.-M. A., Ötting, F., Wendel, A. & Flohé, L. (1984) Hoppe-Seylers Z. Physiol. Chem. 365, 195-212.
36. de Haën, C., Little, S. A., May, J. M. & Williams, R. H. (1978) J. Clin. Invest. 62, 728-737.
37. IUPAC-IUB Joint Commission on Biochemical Nomenclature (JCBN), and Nomenclature Commission of IUB (NC-IUB).Newsletter 1989, Arch. Biochem. Biophys. 272, 262-266 (1989); Biochem. Internat. 20, 209-214 (1989); Bioch. J. 265, I-IV (1989); Biol. Chem. Hoppe-Seyler 370, 1153-1156 (1989); Eur. J. Biochem. 183, 1-4 (1989).
38. IUPAC-IUB Joint Commission on Biochemical Nomenclature (JCBN), and Nomenclature Commission of IUB (NC-IUB).Newsletter 1999, Eur. J. Biochem. 264, 607-609 (1999).
39. IUPAC-IUB Joint Commission on Biochemical Nomenclature (JCBN), and Nomenclature Commission of IUBMB (NC-IUBMB).Newsletter 2009.