3AA-22

Continued from 3AA-20 to 3AA-21

Contents of 3AA-22

3AA-22 Names and Symbols for Derivatives of Named Peptides

• 22.1 Replacement of residues
• 22.2 Extension of the peptide chain
• 22.3 Insertion of residues
• 22.4 Removal of residues
• 22.5 Substitution of side chains of residues
  • 22.5.1 Acylation of a side-chain amino group
  • 22.5.2 Other substituents named as prefixes
  • 22.5.3 Acylation by a side-chain carboxyl group
• 22.6 Partial sequences (fragments)
• 22.7 Peptides with reversed sequence and enantiomers
• 22.8 Peptide analogues
• 22.9 Summary of modification nomenclature

Continued in 3AA appendix

3AA-22. NAMES AND SYMBOLS FOR DERIVATIVES OF NAMED PEPTIDES

It is often convenient to specify the structure of a peptide by reference to a named sequence of which it is a variant. The recommendations that follow allow this, but they apply only to modifications of the sequence involving normal amide links between residues.

Note. To exemplify any named peptide, the imaginary peptide 'iupaciubin' (to symbolize the harmonious co-operation of IUPAC and IUB), Ala-Lys-Glu-Tyr-Leu, is used in formulating the recommendations below. See also the Addendum for the use of seco.

3AA-22.1. Replacement of Residues

In a peptide of trivial name iupaciubin, if the q^th amino-acid residue, starting from the N-terminal end of the chain, is replaced by the amino acid Xaa, the semitrivial name of the modifed peptide is [q-amino acid]iupaciubin, and the abbreviated form is [Xaa^q]iupaciubin. A designation of the chain may be placed before the residue number, e.g. [Ala^B12]insulin(cattle) (see Comment f). Examples:

[8-Citrulline]vasopressin, [Cit⁸]vasopressin

[5-Isoleucine,7-alanine]angiotensin II, [Ile⁵,Ala⁷]angiotensin II

Notes

(a) In the full name, the replacement amino acid is designated by its residue name, not the name of its acyl group (e. g. glycine, not glycyl). This name, and the position of replacement, are given in square brackets.

(b) In the abbreviated form, the amino-acid residues are designated by standard 3-letter symbols (Table 1), the first letter only being a capital (3AA-14), in square brackets.

(c) In the abbreviated form the position of substitution is indicated in a special fashion, i.e. by a superior numeral, to indicate that it is a residue, not an individual atom, that is being replaced.

(d) The residue replaced is not designated in these semitrivial names in order to keep the names short, and because this form of nomenclature of 3AA-22.1 clearly differs from ordinary substitution nomenclature.

(e) The replacement of an amino-acid residue by its enantiomer may be shown by application of this rule as follows: the replacement in iupaciubin of L-tyrosine at position 4 by D-tyrosine results in [4-D-tyrosine]iupaciubin with the abbreviations [D-Tyr⁴]iupaciubin. A mixture of this with iupaciubin gives [4-ambo-tyrosine]iupaciubin or [ambo-Tyr⁴]iupaciubin (3AA-13.2 and 3AA-19.2). Examples: [D-Ser¹]Corticotropin; [D-Asp¹]angiotensin II.

(f) Specification of a sequence may require the species as well as the peptide to be named. If so, the name of the species should be attached, in parenthesis, to the name of the peptide whenever a modifying prefix is present. Thus a substitution in cattle insulin could give [Ala^B12]insulin(cattle). (We prefer 'cattle' as the adjective for this species, since 'bovine' is not used in common speech to designate the species, but to compare human attributes with those of the cow, and 'ox' can be misleading.)

(g) It may be convenient to represent replacement of Gln by Glu or of Asn by Asp with the prefix 'desamido'. Thus [Glu³⁰]corticotropin(pig) could be called desamido³⁰-corticotropin(pig). Similarly replacement of Gla by Glu can be designated with the prefix 'decarboxy'.

3AA-22.2. Extension of the Peptide Chain

The compounds obtained by extension of a peptide at either the N-terminus on the C-terminus are designated by the kinds of names and abbreviations shown below; these are in accordance with general principles of peptide nomenclature (3AA-13.1). Examples:

a) Extension at the N-terminus

Aminoacyliupaciubin Xaa-iupaciubin

Valyliupaciubin Val-iupaciubin

Valylglycyliupaciubin Val-Gly-iupaciubin
(for extension by two residues)

Iupaciubinylamino acid Iupaciubinyl-Xaa

Iupaciubinylleucine Iupaciubinyl-Leu

Note

The enkephalins are the two peptides Tyr-Gly-Gly-Phe-Leu and Tyr-Gly-Gly-Phe-Met. Designations such as Leu-, leucyl- and leucine-enkephalin have been given to the former, with corresponding terms for the latter. These all wrongly imply N-terminal extension, and could not be used together with any indication of such extension. Morley [25] has advocated [Leu]enkephalin, if necessary [Leu⁵]enkephalin, in accordance with 3AA-22.1, implying that enkephalin means Tyr-Gly-Gly-Phe-Xaa. We believe that [Leu⁵]enkephalin is the best designation.

3AA-22.3. Insertion of Residues

The compound obtained by insertion of an additional amino-acid residue Xaa in the position between the q^th and the (q+1)^th residue of the peptide iupaciubin is named endo-qa-amino acid-iupaciubin (abbreviated form: endo-Xaa^qa-iupaciubin). Example:

(a) This form has analogies in other fields where endo implies the insertion of something into a structure (e.g. endo-methylene). The prefix or index qa is based on analogies with the steroids where the atoms inserted into a ring after atom no. q are designated qa, qb, etc.

(b) The prefix 'homo' is not suitable for designating the insertion of a whole residue, especially since it is commonly used to modify the names of individual amino acids, e.g. homoserine (3AA-2.3).

(c) Multiple insertions, and insertion of two or more residues together in the same place in the chain, are shown by a logical extension of this recommendation. Thus the insertion into the peptide iupaciubin of threonine between residues 1 and 2, and of valine and glycine (in that order) between residues 4 and 5, is shown by the name 'endo-1a-threonine,4a-valine,4b-glycine-iupaciubin' and the abbreviation 'endo-Thr^1a,Val^4a,Gly ^4b-iupaciubin'.

3AA-22.4. Removal of Residues

The compound obtained by the formal removal of an amino-acid residue from the peptide iupaciubin in position q is designated by the name des-q-amino acid-iupaciubin, abbreviated des-Xaa^q-iupaciubin. Example:

(a) Removal of a whole residue is indicated in a way similar to that for removal of a ring in steroids, e.g. des-A-androstane.

(b) The form 'de' is not suitable as a prefix because it is easily confused, in speaking, with D (for configuration).

(c) Multiple deletions are designated similarly, e.g. des-Ile³,Asn⁵-oxytocin. If a complete sequence is to be removed, the first and last loci of this sequence are all that need be specified, and they should be put in parentheses with a hyphen between them, e.g. des-(B24-B28)-insulin(mouse).

See also the Addendum for the use of des with seco.

3AA-22.5. Substitution of Side Chains of Residues

The compound formed by introducing an additional amino-acid residue as a substituent of the side chain of a residue in a peptide is named by applying the rules of peptide nomenclature (3AA-7, -9 and -13) to the trivial name, as follows.

22.5.1. Acylation of a Side-Chain Amino Group

If the additional residue acylates an amino group of a peptide, the name of the additional amino acid is written, in its acyl group form (3AA-9.3), and prefixed by symbols indicating the position of substitution (atom and residue number, see 3AA-13.4).

Example: the imaginary compound

derived by acylation of the ε-amino group of the lysine residue at position 2 of iupaciubin (Ala-Lys-Glu-Tyr-Leu) with a valyl group is named N^ε2-valyl-iupaciubin (abbreviated N^ε2-Val-iupaciubin).

22.5.2. Other Substituents Named as Prefixcs

Other substituents that can be named as prefixes are treated similarly to amino acyl groups. Examples:

N^6.2-Methyliupaciubin for

C^4.3-Carboxyiupaciubin for
(alternative to replacement with Gla under 3AA-22.1)

O^4.4-Sulfoiupaciubin or iupaciubin O^4.4-sulfate for

O^4.12-Sulfogastrin or gastrin O^4.12-sulfate for gastrin II.

N^αB1,N^εB29-bis(Boc)insulin or N^2.B1,N^6.B29-bis(Boc)insulin

22.5.3. Acylation by a Side-Chain Carboxyl Group

If an additional amino acid is joined by amide formation between its 2-amino group and the side-chain carboxyl of the peptide iupaciubin, so that the additional amino acid has a free 1-carboxyl group, the derivative is named by specifying the position of substitution (atom and residue number, 3AA-13.4) and it is given the designation 'iupaciubinyl-amino acid'.

Example: the imaginary compound

in which valine is acylated by the [gamma]-carboxyl group of a glutamic residue in position 3 (Glu-3) of iupaciubin (Ala-Lys-Glu-Tyr-Leu), is named N-(iupaciubin-C ^δ3-yl)valine, or N-(iupaciubin-C^5.3-yl)valine, abbreviated to iupaciubin-C^5.3-yl-Val.

Prefixes may also need to be formed from peptide names for use as substituents in other types of compound, as described in 3AA-13.5.

3AA-22.6. Partial Sequences (fragments)

A peptide derived from a named peptide iupaciubin by removal of all residues before the p^th and all after the q^th is named as iupaciubin-(p-q)-peptide. Examples:

From α-melanotropin

we may have

or α-melanotropin-(4-10)-peptide

or, to illustrate the naming of a peptide that contains two fragments, and also a C-terminal amide group:

For oligopeptides it may be convenient to state the length of peptide, e. g. iupaciubin-(2-4)-tripeptide, but this is not normally useful for peptides of over about twelve residues, because the larger multiplying affixes are not widely known. Such a check on the number of residues is particularly useful when two or more sequences are joined, e.g. α-melanotropin-(6-8)-(11-13)-hexapeptide amide.

3AA-22.7. Peptides with Reversed Sequence and Enantiomers

The peptide whose sequence is the reverse of a named peptide may itself be named with the prefix 'retro-', giving retro-iupaciubin from iupaciubin. The enantiomer of a named peptide may be specified with the prefix 'ent-' (a contracted form of enantio-, F-6.4 of [15]), giving ent-iupaciubin from iupaciubin.

3AA-22.8. Peptide Analogues

Analogues of peptides in which the -CO-NH- group that connects two residues is replaced by another group (3AA-19.7) may be indicated by placing ψ in square brackets before the name [25]. The ψ is placed between superscripts indicating the residues modified, and is followed by a comma and the replacing group, e.g. [³ψ⁴,CH₂-S]iupaciubin.

3AA-22.9. Summary of Modification Nomenclature

Click here for "table free" view if the following is faulty.

The application of the principles of 3AA-22 is illustrated in Table 6.

Table 6. Application of the methods of modifying named peptides

Section	Operation	Short name	Structure
-	-	Iupaciubin
22.1	Replacement	[Phe4]iupaciubin
22.2a	Extension (N-terminal)	Arg-iupaciubin
22.2b	Extension (C-terminal)	Iupaciubinyl-Met	Ala-Lys-Glu-Tyr-Leu-Met
22.3	Insertion	Endo-Thr2a-iupaciubin
22.4	Removal	Des-Glu3-iupaciubin
22.5.1	Side-chain substitution on amino group	Nε2-Val-iupaciubin
22.5.2	Side-chain substitution on carboxyl group	Cδ3-Iupaciubinyl-Val
22.6	Partial sequence	Iupaciubin-(2-4)-peptide	Lys-Glu-Tyr
22.7	Reversal of sequence	retro-Iupaciubin	Leu-Tyr-Glu-Lys-Ala
22.7	Enantiomer	ent-Iupaciubin	D-Ala-D-Lys-D-Glu-D-Tyr-D-Leu
22.8	Replacement of CO-NH of peptide bond	[3ψ4,CH2-S]iupaciubin	Ala-Lys-Glu-ψ(CH2-S)-Tyr-Leu
Addendum 3	Partial hydrolysis of a peptide	[seco-3/4]oxytocin

* Square brackets are required to indicate replacement, but are not used for most other modifications.

7. International Union of Biochemistry (1978) Biochemical Nomenclature and Related Documents, The Biochemical Society, London.

12. IUPAC-IUB Commission on Biochemical Nomenclature (CBN), Rules for Naming Synthetic Modifications of Natural Peptides, 1966, Arch. Biochem. Biophys. 121, 6-8 (1967); Biochem. J. 104, 17-19 (1967), corrected 135, 9 (1973); Biochemistry, 6, 362-364 (1967); Biochim. Biophys. Acta, 133, 1-5 (1967); Bull. Soc. Chim. Biol. 49, 325-330 (1967) (in French); Eur. J. Biochem. 1, 379-381 (1967), corrected 45, 3 (1974); Hoppe-Seyler's Z. Physiol. Chem. 348, 262-265 (1967) (in German); J. Biol. Chem. 242, 555-557 (1967); Mol. Biol. 2, 466-469 (1968) (in Russian); Pure Appl. Chem. 31, 647-653 (1972); also pp. 85-87 in [7].

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.

15. IUPAC Commission on the Nomenclature of Organic Chemistry (CNOC). Nomenclature of Organic Chemistry, Section F: Natural Products and Related Compounds, Recommendations 1976, Eur. J. Biochem. 86, 1-8 (1978); also pp. 151-26 in [7] and pp. 491-511 in [14]. [See also Biochemical Nomenclature and Related Documents, 2nd edition, Portland Press, 1992, pages 19-26.]

25. Morley, J. S. (1981) Neuropeptides, 1, 231-235.

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