Orexin A

1 Identity

Synthetic 33-residue peptide, N-terminal pyroglutamate, C-terminal amide, two intrachain disulfide bridges. Constitutionally identical to the mature endogenous neuropeptide. At 33 residues it sits just below the 40-amino-acid line and is therefore a drug rather than a biological product. orexin-A (human, bovine, mouse, rat - the mature peptide is identical across these species). Not a synonym for Orexin B / hypocretin-2.

Sequence

PGlu-Pro-Leu-Pro-Asp-Cys-Cys-Arg-Gln-Lys-Thr-Cys-Ser-Cys-Arg-Leu-Tyr-Glu-Leu-Leu-His-Gly-Ala-Gly-Asn-His-Ala-Ala-Gly-Ile-Leu-Thr-Leu-NH2. Thirty-three residues, all L. Three modifications, all structural rather than optional: (a) the N-terminus is pyroglutamate, a cyclized glutamine, which blocks Edman degradation outright so N-terminal sequencing is unavailable and MS/MS carries the identity burden - a certificate offering Edman data on this molecule is evidence about the document rather than about the lot; (b) the C-terminus is an amide on Leu33; (c) four cysteines form two intrachain disulfide bridges, Cys6-Cys12 and Cys7-Cys14. The disulfide pattern is the analytically decisive feature of this molecule: four cysteines admit three possible pairwise connectivities, all three of which are exactly isobaric, so intact mass proves that two bridges formed and proves nothing whatever about where. Connectivity is therefore a named certificate attribute on this article, and intact mass is expressly refused as proof of folding. No D-residues, no non-proteinogenic residue other than the pyroglutamate, no lipid, no PEG, no metal.

Molecular formula

C152H243N47O44S4 (free base, both disulfides formed, C-terminal amide, N-terminal pyroglutamate). The fully reduced dithiol form of the same sequence is C152H247N47O44S4.

Average mass

3561.141 Da from C152H243N47O44S4 on IUPAC 2021 abridged conventional atomic weights. One reagent catalog prints 3561.1 under CAS 205640-90-0, and calculation from the primary structure reproduces it, which is what makes the published figure usable as a specification rather than as a quotation. The fully reduced form is 3565.173, exactly 4.032 average higher.

Monoisotopic mass

3558.7105 Da neutral monoisotopic from C152H243N47O44S4. [M+2H]2+ 1780.3625; [M+3H]3+ 1187.2441; [M+4H]4+ 890.6849 - and the multiply charged ions are the practical ones, because a peptide of this size is measured on an electrospray charge-state envelope rather than as a singly protonated ion. The fully reduced dithiol form is 3562.7418 monoisotopic, exactly +4.0313; a single unformed bridge is exactly +2.0157.

Salt / variant note

The principal risk on this molecule is not substitution but misfolding, and it is invisible to mass. (1) The two disulfide-scrambled connectivity isomers - Cys6-Cys7 with Cys12-Cys14, and Cys6-Cys14 with Cys7-Cys12 - share the formula C152H243N47O44S4 and therefore share the average 3561.141 and the monoisotopic 3558.7105 exactly. No mass measurement at any resolving power separates them from the correct Cys6-Cys12 / Cys7-Cys14 article. Only non-reduced peptide mapping with disulfide-bridged fragment assignment does. Two of the three possible connectivities are wrong and both are isobaric with the right one. (2) The fully reduced dithiol form, C152H247N47O44S4, avg 3565.173 / mono 3562.7418, exactly +4.0313 monoisotopic; a partially oxidized single-bridge species sits at exactly +2.0157. Both are detectable by mass and by a free-thiol assay, and both are release failures. (3) Intermolecular disulfide dimers and higher oligomers, at approximately twice the monomer mass less 2.016 per new bridge, seen by SE-HPLC and by non-reduced SDS-page rather than by intact mass in isolation. (4) The unclosed N-terminal glutamine species, +17.0265 relative to the pyroglutamate article, arising where cyclization is incomplete; and the glutamate species, +18.0106, where hydrolysis has occurred instead. (5) The C-terminal free acid of the same sequence, -0.984, invisible on any nominal-mass reading of a molecule this size and effectively invisible on a low-resolution charge-state envelope too. (6) Orexin B / hypocretin-2, a 28-residue amidated peptide from the same precursor, sold under an adjacent name; it is a different article with a different mass and must never be released against this specification. (7) Methionine is absent from this sequence, which removes the usual oxidation liability, but two histidines, one tyrosine and four cysteines remain, and cysteine oxidation to sulfinic and sulfonic acid at +31.990 and +47.985 is the relevant degradation family here.

2 Class & testing panel

Form

Single article

Testing panel

P1 — panel definition

3 Primary sources & evidence

The index reports the design and provenance of the literature, not a conclusion about effect.

Published literature exists and is substantial; it is reported here by study type and identifier only. The peptide was described in 1998 in two independent reports: de Lecea L et al., Proc Natl Acad Sci USA 1998;95:322-327 (hypocretin nomenclature) and Sakurai T et al., Cell 1998;92:573-585 (orexin nomenclature) - the dual naming of this article dates from those two papers and is the reason the catalog carries both names on the same record. The literature that followed is predominantly rodent neurophysiology and receptor pharmacology, together with a large canine and human genetics literature in narcolepsy from 1999 onward. Human interventional work with the peptide itself is limited by delivery and is chiefly intranasal, small and largely from a small number of groups; the clinically advanced orexin-receptor programs are non-peptide oral small molecules and belong to different records, a distinction the citation index marks explicitly because conflating them is the standard error in the gray-market literature on this compound. No FDA-approved product contains this peptide.

4 Storage & specification

Storage

White lyophilized solid in Type I amber glass under nitrogen, stoppered and crimped. Store at -20 degrees C plus or minus 5 degrees C for routine holding, or -80 degrees C where a lot is designated as a reference standard; desiccated over silica, protected from light. Inert headspace matters here for the opposite reason to the methionine-containing articles in this catalog: it is not oxidation of a side chain that is feared but thiol-disulfide exchange, which is base- and moisture-catalyzed and which scrambles connectivity without changing the mass. Equilibrate the sealed vial to room temperature before opening. The material is not stored reconstituted; where a solution is unavoidable it is single-use, prepared in a stated buffer at a stated pH below neutral, and the vial label says so. Ships frozen with a validated shipper and a single-use temperature logger in every carton; freeze-thaw cycles are counted and limited on the label.

Shelf life

Provisional 24-month retest interval at -20 degrees C plus or minus 5 degrees C, desiccated and light-protected, stated as provisional pending this company's own stability data. The stability-indicating attributes are not assay and not total related substances but, in order: disulfide connectivity by non-reduced peptide map, free thiol, aggregate percentage by SE-HPLC, and water. That ordering follows from the chemistry - a lot of this article fails by scrambling or by dimerizing long before it fails by losing assay. The confirming study is an ICH Q1A(R2) design at 0, 3, 6, 9, 12, 18 and 24 months at -20 degrees C, with 2 to 8 degrees C and 25 degrees C / 60 percent RH arms, and the peptide map repeated at the 12-month and terminal points rather than only at time zero. Printed retest date on every vial, first-expiry-first-out enforced against it.