MOTS-c

1 Identity

Mitochondrial-derived and mitochondria-targeting peptides. A plain linear synthetic 16-residue peptide whose open reading frame is encoded within the mitochondrial 12S ribosomal RNA gene and read in the mitochondrial genetic code. Species and fragment designations are part of the identity and not decoration: 'MOTS-c (human)', 'MOTS-c (rat)', 'MOTS-c (mouse)', 'MOTS-c (1-12)' and 'MOTS-c (1-13)' are five different articles cataloged under the same three-word name by a single institutional supplier.

Sequence

H-Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg-OH; one-letter MRWQEMGYIFYPRKLR, 16 residues, free acid. All-L, entirely proteinogenic. Free N-terminal alpha-amine, free C-terminal carboxylic acid, no acetylation, no amidation, no acylation, no PEG, no D-residue, no non-proteinogenic residue, no cysteine and no disulfide. The oxidation inventory is the specification for this sequence and the positions must be stated correctly: two methionines at positions 1 and 6 - not 1 and 5 - one tryptophan at position 3, and two tyrosines at positions 8 and 11. That inventory makes oxidation the principal degradation route for this sequence and it is why inert headspace is a release condition rather than a packaging preference. Three arginines and one lysine make the counterion burden significant and it is identified and quantified per lot.

Molecular formula

C101H152N28O22S2 (free acid, salt-free). Mono-acetate C103H156N28O24S2. Mono-trifluoroacetate C103H153F3N28O24S2. Mono-sulfoxide C101H152N28O23S2. Species and fragment articles: rat C113H183N33O28S2; mouse C69H99N13O17S2; (1-12) C77H105N17O18S2; (1-13) C83H117N21O19S2. K14Q polymorph peptide C100H148N28O23S2.

Average mass

2,174.621 Da (C101H152N28O22S2), from the formula on IUPAC 2021 abridged conventional atomic weights. One supplier prints 2174.61 for its catalog entry, and the computed value reconciles with that printing to 0.01 Da. Salt arithmetic as A check on the supplier: a reagent catalog prints C101H152N28O22S2 . CF3COOH with formula weight 2288.6, and the in-house mono-trifluoroacetate computes to 2,288.64 - the difference from the free acid is 114.02, exactly one trifluoroacetate, so that catalog's own printed salt weight validates the free-acid figure. Mono-acetate 2,234.67. Comparators: rat 20-mer 2,516.03; mouse 11-mer 1,446.75; (1-12) 1,620.91; (1-13) 1,777.10; K14Q 2,174.58; mono-sulfoxide 2,190.62.

Monoisotopic mass

2,173.10774 Da neutral (C101H152N28O22S2). Working ions: [M+2H]2+ m/z 1,087.56115; [M+3H]3+ m/z 725.37652. Comparators: rat 2,514.33517; mouse 1,445.67233; (1-12) 1,619.72649; (1-13) 1,775.82760; mono-sulfoxide 2,189.10265 (+15.99491). K14Q 2,173.07135 - 0.03639 Da from the parent on the neutral mass and 0.01213 Da apart on the 3+ ion, which demands a resolving power near 1 part in 60,000 at that m/z. That substitution is invisible to any certificate that stops at accurate mass, and only LC-MS/MS coverage across residue 14, or an amino acid analysis Lys:Gln ratio, excludes it.

Salt / variant note

Five chemically distinct molecules are sold under the name 'MOTS-C' by one institutional supplier alone, and none of them is a fraud - they are species and fragment variants that a purchase order must specify. (1) human parent, MRWQEMGYIFYPRKLR, C101H152N28O22S2, 2,174.62 average / 2,173.10774 monoisotopic (printed MW 2174.61). (2) MOTS-c (rat), MKRKEMGYIFFSQRTLRNPL - a 20-residue peptide sharing only eight residues with the human sequence - C113H183N33O28S2, 2,516.03 / 2,514.33517 (printed 2516.02). (3) MOTS-c (mouse), MKWEEMGYIFL, 11 residues, C69H99N13O17S2, 1,446.75 / 1,445.67233 (printed 1446.74). (4) MOTS-c (1-12), MRWQEMGYIFYP, C77H105N17O18S2, 1,620.91 / 1,619.72649 (printed 1620.9); and MOTS-c (1-13), MRWQEMGYIFYPR, C83H117N21O19S2, 1,777.10 / 1,775.82760. Every computed value matches the corresponding printed figure to within 0.03 Da. (5) salt basis: one catalog lists 'MOTS-c (human)' and 'MOTS-c (human) acetate' as two separate items and another ships the trifluoroacetate at about 5.0 percent w/w counterion - three declared bases in the market, computing to 2,174.62 free acid, 2,234.67 mono-acetate and 2,288.64 mono-trifluoroacetate. (6) MOTS-c K14Q, the peptide encoded by the naturally occurring m.1382A>C polymorphism, C100H148N28O23S2, 2,174.58 / 2,173.07135 - 0.036 Da from the parent on the neutral mass, 0.012 Da apart on the 3+ ion, requiring roughly 1 part in 60,000 resolving power. Invisible to any certificate that stops at accurate mass. (7) oxidation states arriving as impurities with the same +15.99491 Da arithmetic at Met1 and Met6, plus the Trp3 series: +15.99491 hydroxytryptophan, +31.98983 N-formylkynurenine, +3.99491 kynurenine.

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, is real and growing, and is almost entirely preclinical. The originating paper - Lee C, Zeng J, Drew BG, et al., Cell Metabolism 2015;21:443-454 - is mouse and cell-culture work. The several hundred citations since are predominantly rodent, cell-culture and observational human-genetics studies, including work on the m.1382A>C mitochondrial polymorphism in Japanese cohorts, which is the same polymorphism that generates the K14Q variant peptide noted above. Human interventional data on administered synthetic MOTS-c is essentially absent: one analog entered early-phase clinical study, and that analog is a different molecule whose trial record does not transfer to this one. Exercise-physiology papers reporting circulating MOTS-c concentrations are observational measurements of an endogenous peptide, not administration studies, and the citation index badges them as such rather than counting them as clinical evidence. Every statement in this section describes the retrieved literature and its study types.

4 Storage & specification

Storage

Lyophilized solid, stored at -20 degrees C plus or minus 5 degrees C, desiccated over silica, protected from light, sealed under argon or nitrogen, in an amber borosilicate vial with a fluoropolymer-faced closure; non-sterile, with no sterility claim. The inert headspace is not decoration: Met1, Met6 and Trp3 make atmospheric oxygen the principal degradation route for this sequence, and a vial held open-headspace at 2 to 8 degrees C will breach its own oxidation limits before it breaches its purity limit. The headspace condition is therefore a release-relevant instruction, is stated on the certificate, and a failed seal is treated as an out-of-trend event in its own right rather than as a packaging defect. Vials are equilibrated to ambient temperature before opening. Reconstituted solution is aliquoted single-use, held at -80 degrees C and protected from light; repeated freeze-thaw with air ingress is the fastest available route to an out-of-specification oxidation result in the buyer's own hands.

Shelf life

Provisional 24-month retest interval at -20 degrees C plus or minus 5 degrees C under inert headspace, desiccated, stated as provisional pending the company's own stability data. The confirming study is an ICH Q1A(R2)-style design in which the oxidation impurities are the stability-indicating attributes rather than gross purity: pulls 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 relative humidity arms to set shipping and short-excursion limits, and with methionine sulfoxide at positions 1 and 6 and each Trp3 oxidation product reported individually at every pull. A headspace-integrity check accompanies every pull, because the nitrogen or argon blanket is part of the specification and a failed seal is the likeliest single cause of an out-of-trend oxidation result. The label carries the retest date, and material reaching it is re-assayed against the same oxidation attributes before any re-dating.