CJC-1295 vs. Sermorelin: A Structural Comparison

All three are analogues of GRF(1-29): the first 29 residues of a 44-residue human peptide, growth hormone-releasing factor, abbreviated GRF or GHRH. That expansion is nomenclature — it is how the fragment is identified in chemical catalogues — and nothing in this article turns on it.

Sermorelin

• Synonyms: GRF(1-29), GHRH(1-29)
• Sequence: YADAIFTNSYRKVLGQLSARKLLQDIMSR-NH₂ — 29 residues, C-terminal amide
• Formula: C₁₄₉H₂₄₆N₄₄O₄₂S  ·  MW: 3,357.9 g/mol
• CAS: 86168-78-7  ·  PubChem CID: 16132413

CJC-1295 without DAC

• Synonyms: Modified GRF(1-29), Mod GRF 1-29, CJC-1295 DAC-free
• Structure: GRF(1-29) amide with four substitutions — D-Ala², Gln⁸, Ala¹⁵, Leu²⁷
• Formula: C₁₅₂H₂₅₂N₄₄O₄₂  ·  MW: 3,367.9 g/mol
• CAS: 863288-34-0  ·  PubChem CID: 56841945

CJC-1295 with DAC

• Synonyms: DAC:GRF, CJC-1295 DAC
• Structure: the same tetrasubstituted 29-residue chain, extended with a Lys³⁰ whose side-chain amine carries a 3-maleimidopropionyl group
• Formula: C₁₆₅H₂₆₉N₄₇O₄₆  ·  MW: 3,647.2 g/mol
• CAS: 446262-90-4  ·  PubChem CID: 91971820

A listing that says only "CJC-1295" has not specified which of the last two it is selling. The molecular weight on the paperwork resolves it immediately: 3,367.9 or 3,647.2.

Every difference between sermorelin and the modified chain is one of these four, and each has a specific chemical rationale.

• Ala² → D-Ala². A change of stereochemistry only, from the L-enantiomer to the D-enantiomer. Dipeptidyl peptidase-IV is an exopeptidase that removes N-terminal dipeptides where the second residue is alanine or proline, and its active site is stereospecific; a D-residue at that position makes the bond a poor substrate. This is an enzymatic-stability substitution, and it changes no atom counts at all.
• Asn⁸ → Gln⁸. Asparagine is the residue most prone to deamidation, and replacing it with glutamine — which deamidates far more slowly — removes the most labile chemical liability in the chain. Adds one CH₂: +14.03 Da.
• Gly¹⁵ → Ala¹⁵. Glycine, lacking a side chain, is the most conformationally permissive residue and the strongest helix breaker; alanine is the strongest helix former. The substitution stiffens the backbone locally and raises helical propensity in that region. Also adds one CH₂: +14.03 Da.
• Met²⁷ → Leu²⁷. This removes the molecule's only methionine, and with it the only sulfur atom. Methionine oxidises readily to the sulfoxide, a +16 Da modification that is one of the commonest storage defects in peptide chemistry. Leucine is isosteric and inert. The exchange of sulfur for CH₂ is −18.04 Da.

The arithmetic reconciles exactly, which is a useful check on any certificate quoting these compounds:

3,357.9 + 14.03 + 14.03 − 18.04 = 3,367.9 g/mol

So does the formula: C₁₄₉H₂₄₆N₄₄O₄₂S, plus three CH₂ and minus one S, gives C₁₅₂H₂₅₂N₄₄O₄₂.

Note the practical consequence of the fourth substitution: sermorelin carries a methionine and the modified chain does not, so sermorelin has an oxidation liability its analogue lacks. That affects how each should be handled — see peptide storage and handling — and it also rules out DMSO as a solvent for sermorelin, per the solubility guide.

DAC stands for drug affinity complex, and structurally it is a piece of standard bioconjugation chemistry: a 3-maleimidopropionyl group amide-linked to the ε-amine of an added Lys³⁰.

The maleimide ring is a thiol-selective Michael acceptor. Presented with a free sulfhydryl group it undergoes conjugate addition across the ring's double bond to form a stable thioether bond. This is the same reactive handle used throughout protein labelling and antibody conjugate work, chosen because it is fast, essentially selective for thiols over amines at mildly acidic to neutral pH, and forms a covalent linkage.

The mass contribution is straightforward: a lysine residue at 128.17 g/mol plus a maleimidopropionyl acyl group at 151.12 g/mol, giving the 279.3 g/mol that separates the two CJC-1295 variants. On the formula, C₁₅₂H₂₅₂N₄₄O₄₂ plus C₆H₁₂N₂O plus C₇H₅NO₃ gives C₁₆₅H₂₆₉N₄₇O₄₆.

Handling Consequences of a Maleimide

Carrying a reactive group changes what the material can safely touch, and this is genuinely different from handling an unmodified peptide:

• Keep it away from free thiols. Reducing agents such as DTT, TCEP and 2-mercaptoethanol, and any buffer containing them, will quench the maleimide irreversibly.
• Avoid alkaline conditions. The maleimide ring hydrolyses to the corresponding maleamic acid, which is unreactive toward thiols. Ring-opening accelerates sharply above pH 8, so mildly acidic to neutral is the working range.
• Hydrolysis is a mass change of +18 Da, which means ring-opened material is detectable by mass spectrometry as a distinct species rather than being silently present.

All three are strongly basic. Counting the ionisable groups on sermorelin at around pH 7: three arginines, two lysines and a free N-terminal amine give +6, against two aspartates at −2, with no contribution from the C-terminus because it is an amide rather than a free acid. Net charge is approximately +4, and the isoelectric point sits high, in the region of pH 10.

The tetrasubstituted chain has the same ionisable set — none of the four substitutions touches a charged residue — so it too carries net +4. The DAC variant adds a lysine, but that lysine's side-chain amine is acylated by the linker and contributes no charge, so it also remains at approximately +4 while gaining 279.3 g/mol of mass.

In practice all three dissolve readily in water, as a strongly basic and largely hydrophilic sequence should. The corollary of that charge density is a substantial counter-ion load after reversed-phase purification, so net peptide content matters here; the purity vs. content guide covers the correction. All three are supplied as lyophilised solids in sealed vials at milligram scale.

By electrospray mass spectrometry these are large enough that multiply charged ions dominate. Sermorelin at 3,357.9 g/mol gives [M+3H]3+ near m/z 1,120.3; the DAC-free analogue at 3,367.9 gives [M+3H]3+ near m/z 1,123.6; the DAC variant at 3,647.2 gives [M+3H]3+ near m/z 1,216.7.

Two observations follow, and the second is the important one.

First, the DAC variant is trivially distinguishable — 279.3 Da is an enormous gap and no instrument will miss it. Sermorelin and the DAC-free analogue differ by only 10.0 Da on a base of roughly 3,360, or 0.3%, which is a 3.3-unit separation at the 3+ charge state: resolvable on a competent instrument from a deconvoluted mass, but not something to eyeball off a low-resolution spectrum.

Second, and more consequentially: the D-Ala² substitution is isobaric. D-alanine and L-alanine have identical mass, so no mass measurement of any resolution can confirm that the substitution is present. A certificate reporting an observed mass of 3,367.9 confirms the composition of the modified chain; it does not confirm the stereochemistry, which is the substitution the analogue is defined by. Establishing that requires chiral analysis — typically hydrolysis followed by chiral chromatography or derivatisation with a chiral reagent — which is not part of a routine peptide certificate.

This is a clean illustration of the general point in HPLC vs. mass spectrometry: mass establishes composition, not arrangement. Reversed-phase chromatography partially compensates, since diastereomers frequently differ in retention time, but the two methods together still leave stereochemical identity as an inference rather than a measurement.

Current listings and composition data are on the Sermorelin product page and across the research peptides catalogue.

• HPLC vs. Mass Spectrometry
• Peptide Storage and Handling
• Peptide Glossary
• Sermorelin 5mg
• Shop Research Peptides