PT-141 and bremelanotide are the same molecule under two names, which is the first thing that trips people up. The second is that it is cyclic. That single structural feature changes how it is made, how it behaves on a column, and what it takes to prove that a vial contains what the label says.

Identity on paper

  • CAS number: 189691-06-3
  • Molecular formula: C50H68N14O10
  • Molecular weight: approximately 1,025 g/mol
  • PubChem CID: 9941379

PT-141 is the research shorthand and bremelanotide the nonproprietary name. Neither is an identifier in the way the formula and the CAS number are, which is the argument for reading a certificate rather than a label.

Where the structure comes from

PT-141 belongs to a lineage of melanocortin peptides that began with modified analogues of the natural hormone. A key step in that lineage was the design of cyclic analogues in which a bridge between two side chains locks the backbone into a constrained shape, a strategy introduced in the late 1980s and shown to produce markedly more potent compounds than their flexible counterparts. (Reference: Al-Obeidi et al., 1989)

The bridge itself

The usual way to constrain a peptide of this kind is a side-chain to side-chain lactam: an amide bond formed between the amine on one side chain and the carboxyl on another, several positions apart in the sequence. It is the same kind of bond that links the backbone, built in a different place.

A disulfide bridge would also close a ring, but it can be reduced and reopened. A lactam cannot, so the constraint holds under conditions that would undo a disulfide. That stability is why the strategy became standard for this family.

What cyclisation does

Closing a peptide into a ring has three consequences that matter in the laboratory, and none of them are about potency.

  • It restricts conformation. A linear chain samples many shapes. A constrained ring holds a narrower set, which is the point of making it.
  • It removes chain ends. Enzymes that chew inward from a free terminus have nothing to grip, so cyclic peptides are generally more resistant to that route of degradation.
  • It changes chromatographic behaviour. The folded, constrained form presents a different surface to a reversed-phase column than the open chain would, so retention time is not predictable from sequence alone.

Our note on cyclic and linear peptides covers the general case.

The melanocortin receptors

The melanocortin family comprises several receptor subtypes distributed across different tissues and associated with a range of signalling processes, and the physiology has been reviewed in detail. (Reference: Cone, 2006) Because the family has several members with overlapping ligand preferences, the recurring research question for any melanocortin agonist is selectivity: which subtypes it engages and how strongly, relative to the others. Our note on melanocortin receptors introduces the family, and the general distinction between agonists and antagonists is covered separately.

This is laboratory and model-based work. PT-141 is supplied strictly as a research compound, and nothing here describes use in people or animals.

The verification problem cyclic peptides create

This is the part that is rarely mentioned and is worth knowing. Forming a ring is a condensation: a bond is made and a molecule of water is released. The cyclic product therefore weighs about eighteen daltons less than the linear precursor it came from.

Eighteen daltons is an easy difference to measure, so a simple mass check will tell you whether cyclisation happened. What a single mass measurement will not tell you is where the ring closed, if more than one pair of side chains could have reacted, because every one of those products has the same formula and the same mass. Distinguishing them requires fragmentation, which is what tandem mass spectrometry provides. A certificate that reports a matching mass has answered a real question, not every question.

Making it

The chain is assembled by solid-phase synthesis like any other sequence, and the cyclisation is an additional step with its own yield. Run at high concentration, chains tend to react with each other rather than with themselves, producing dimers and larger species instead of the intended ring. Those by-products are part of what a purity method has to separate, which is one reason a cyclic peptide is more than a linear peptide with one more step.

When the ring is closed

Cyclisation can be done while the chain is still attached to the resin or after it has been cleaved into solution. On-resin has a practical advantage: the beads keep the chains physically separated, so a chain is more likely to find its own other end than a neighbour's. In solution the same reaction has to be run dilute to achieve the same effect, which means large volumes for small amounts of product.

Either way the step has a yield, and whatever did not cyclise correctly is still in the mixture when purification begins.

Handling and verification

Material ships lyophilized, which is the stable form, and the usual rule applies: keep it dry, keep it cool, and let a cold vial warm before opening so condensation does not form inside. Purity is established by HPLC and identity by mass spectrometry, and any Codex Research vial can be checked against its paperwork by batch number.

One detail specific to this compound is worth carrying into the paperwork. Because part of the analytical question is whether the ring closed and closed in the right place, a certificate for a cyclic peptide that reports only a purity percentage is answering less than it appears to. The identity line is doing more work here than it does for a linear sequence.

Research use only

All products sold by Codex Research, including PT-141, are strictly for laboratory research and development. They are not for human or animal consumption and are not intended to diagnose, treat, cure, or prevent any disease.

The compound at Codex Research

PT-141, 10 mg per vial · batch-verified, with its certificate of analysis.

Frequently asked questions

Are PT-141 and bremelanotide the same thing?

Yes. PT-141 is the research shorthand and bremelanotide is the nonproprietary name for the same synthetic peptide, CAS 189691-06-3, formula C50H68N14O10. It is supplied strictly for laboratory research.

What does it mean that PT-141 is a cyclic peptide?

A bridge between two side chains closes the backbone into a ring. That restricts the shapes the molecule can adopt, removes the free chain ends that some enzymes degrade from, and changes how it is retained on a reversed-phase column.

What receptors does PT-141 act on?

It acts as an agonist at melanocortin receptors, a family of several subtypes distributed across different tissues and associated with a range of signalling processes. Because the subtypes have overlapping ligand preferences, selectivity is the recurring research question.

Why does a cyclic peptide weigh less than its linear precursor?

Because forming the ring is a condensation. A bond is made and a molecule of water is released, so the cyclic product is about eighteen daltons lighter than the open chain it was made from.

Can mass spectrometry confirm where a peptide cyclised?

Not from a single mass measurement. If more than one pair of side chains could have reacted, every possible product has the same formula and the same mass. Telling them apart requires fragmentation, which tandem mass spectrometry provides.

What by-products does cyclisation produce?

Mainly dimers and larger species, formed when chains react with each other instead of closing on themselves. They are part of what a purity method has to separate, which is why cyclisation is more than one extra step.

References

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