MVT-602: Molecular Structure

Molecular Structure and Properties#

MVT-602 (TAK-448) is a synthetic nonapeptide designed as a metabolically stabilized analog of the C-terminal active fragment of kisspeptin. It has a molecular weight of 1225.36 Da, molecular formula C58H80N16O14, and CAS number 1234319-68-6. The peptide was developed through structure-activity relationship optimization to achieve potent KISS1R agonism with significantly extended duration of action compared to native kisspeptin peptides.

Amino Acid Sequence#

The primary structure of MVT-602 is:

Ac-D-Tyr-Hyp-Asn-Thr-Phe-azaGly-Leu-Arg(Me)-Trp-NH2

This represents a 9-residue peptide with the following modifications from the native kisspeptin C-terminal decapeptide (kisspeptin-10: Tyr-Asn-Trp-Asn-Ser-Phe-Gly-Leu-Arg-Phe-NH2):

• N-terminal acetylation (Ac-): Blocks aminopeptidase-mediated degradation
• Position 1 (D-Tyrosine): D-configuration provides resistance to N-terminal exopeptidases
• Position 2 (Hydroxyproline, Hyp): Replaces native asparagine; hydroxyproline is a constrained amino acid that stabilizes the peptide backbone conformation and resists general proteolysis
• Position 6 (azaGlycine): Replaces native glycine with azaglycine (a nitrogen atom replaces the alpha-carbon), providing backbone rigidity and protease resistance
• Position 8 (Methylated Arginine, Arg(Me)): N-methylation of the arginine guanidinium group enhances metabolic stability
• C-terminal amidation (-NH2): Standard peptide modification that improves receptor binding and prevents carboxypeptidase degradation

Receptor Pharmacology#

MVT-602 is a potent and full agonist of the KISS1R (also known as GPR54) receptor:

• IC50: 460 pM (receptor binding)
• EC50: 632 pM (functional activation)
• Selectivity: Highly selective for KISS1R with no significant activity at other GPCRs

The binding interaction involves the C-terminal residues (particularly Phe, Leu, Arg, Trp) engaging the KISS1R transmembrane binding pocket in a manner similar to the native kisspeptin C-terminal decapeptide. The non-standard amino acid modifications primarily enhance metabolic stability without significantly compromising receptor affinity.

Pharmacokinetics#

MVT-602 was designed to achieve a longer duration of action than native kisspeptin-54:

• Half-life: Approximately 108 minutes (compared to approximately 28 minutes for kisspeptin-54)
• Route: Subcutaneous injection
• Time to peak LH: 21-22 hours (versus 4.7 hours for kisspeptin-54)
• LH AUC enhancement: Approximately 4-fold greater than kisspeptin-54

The approximately 4-fold extension in half-life compared to kisspeptin-54 translates to a disproportionately large pharmacodynamic enhancement because the sustained KISS1R activation allows for continued GnRH pulsatility and a more complete LH surge mimicking the natural mid-cycle ovulatory signal.

Comparison with Kisspeptin-54#

Stability#

As a modified peptide with multiple non-standard amino acids, MVT-602 demonstrates enhanced stability compared to native kisspeptin:

• Proteolytic resistance: D-Tyr, Hyp, azaGly, and Arg(Me) modifications collectively protect against endopeptidases, exopeptidases, and trypsin-like proteases
• Formulation: Administered as a subcutaneous injection solution; specific formulation details have not been publicly disclosed
• Storage: Clinical trial supply handled under controlled conditions; commercial storage requirements not established

Related Reading#

• MVT-602 overview and research guide
• Peptides similar to MVT-602
• MVT-602 research evidence