Chemical identifiers glossary: CAS, UNII, PubChem CID and InChIKey for peptide records

Why one peptide needs several identifiers

Names are unreliable. PubChem lists synonyms for oxytocin including brand names, translations, code names and a structural name such as (1-Hemicystine)oxytocin, all in one list. [4] A literature search on one name, an inventory entry under another and a supplier listing under a third may or may not describe the same compound. Identifiers fix that, but only if you know what each one encodes.

This guide covers the identifiers you are most likely to meet on a peptide certificate, safety data sheet or database record, and how to cross-walk them for one molecule. It uses oxytocin as the example because its public records are complete; nothing here concerns its use.

The identifier systems

CAS Registry Number: assigned in sequence by CAS, which calls itself the source and final authority for these numbers. CAS says the registry holds more than 300 million substances, that a number of up to 10 digits in three hyphenated parts identifies a substance and avoids confusion from multiple names, and that the right-most digit is a check digit. CAS Common Chemistry is an open community resource with nearly 500,000 substances; CAS Registry Services can supply more obscure numbers for a fee. [3]

UNII: the Unique Ingredient Identifier generated by FDA Global Substance Registration System, developed with NIH NCATS and the EMA, and used in electronic listings such as DailyMed. [1] precisionFDA states that UNIIs are generated from scientific identity characteristics using ISO 11238 data elements and that UNII availability does not imply any regulatory review or approval. [2]

PubChem CID: a compound record in NCBI PubChem. Salt forms get their own CID, and PubChem links each to a parent: a parent lookup for oxytocin acetate (CID 12004215) returns oxytocin (CID 439302). [5] [6] [7]

InChIKey: a 27-character hashed form of the IUPAC International Chemical Identifier. The first 14-character block encodes core constitution (formula, connectivity, hydrogens, charge); the second 8-character block encodes stereochemistry and isotopes; a flag shows standard or non-standard InChI; the last character shows protonation. Because it is a hash, a structure cannot be restored from the key, and the authors note that collisions, two structures sharing one key, cannot be ruled out entirely. [9] IUPAC maintains oversight of InChI, which is non-proprietary. [10]

ChEBI and UniProt: database records at EMBL-EBI and UniProt. ChEBI gives formula, average and monoisotopic mass and InChIKey; UniProt gives the biological sequence and its modifications for natural peptides. [8] [11]

Worked cross-walk: oxytocin

PubChem lists CAS 50-56-6, UNII 1JQS135EYN, ChEBI CHEBI:7872 and DTXSID8048361 among the synonyms for CID 439302, along with 200-048-4, which looks like a CAS number but is the European Community (EC) number that PubChem files under a separate heading. [4] [12] PubChem gives the InChIKey XNOPRXBHLZRZKH-DSZYJQQASA-N and ChEBI gives the same key, which confirms both records describe one structure. [5] [8] UniProt P01178 records oxytocin as residues 20 to 28 of a precursor. [11]

Oxytocin acetate (CID 12004215) has InChIKey DSZOEVVLZMNAEH-BXUJZNQYSA-N: both the 14-character first block and the 8-character second block differ, because adding acetic acid changes the formula. [6] A search on the free-peptide InChIKey will not find the salt record, and vice versa. The parent link is how you join them. [7]

Using the InChIKey blocks to find stereo variants

Because the first block encodes connectivity and the second block encodes stereochemistry, two stereoisomers with the same connectivity share the first 14 characters and differ in the second block. [9] Searching on the first block alone is a quick way to find records for diastereomers or for structures with stereochemistry left undefined. Treat hits as leads; the hash can collide, and a record with undefined stereochemistry is not the same as a specific isomer.

The same rule explains a common mismatch: a supplier who registers a peptide without stereo information gets a different InChIKey second block from the PubChem record. That is a documentation gap, not proof of a different product, but it is worth asking about.

Inventory record checklist

Store identifiers as fields, not in a free-text name. Keep the source and date for each, because synonym lists change.

• Record the PubChem CID for the exact form you hold (free peptide or salt) and its parent CID.
• Record the InChIKey from the same PubChem record and check it matches ChEBI where one exists.
• Record CAS and UNII as given by the supplier and as found in PubChem; note any disagreement.
• For natural sequences, record the UniProt accession and residue range.
• Never treat a UNII, CAS number or PubChem record as evidence of approval, purity or supplier quality.
• Search literature by CID or InChIKey as well as by name.