CJC-1295 (without DAC) vs Kisspeptin

CJC-1295 (without DAC)

CJC-1295 without DAC, also called modified GRF (1-29), is a 29-residue synthetic analogue of growth hormone-releasing hormone (GHRH). Native GHRH has 44 residues, but its first 29 carry the receptor-binding activity, and this peptide is built on that shortened sequence with four amino-acid substitutions intended to slow breakdown. The name causes confusion: CJC-1295 originally referred to a version carrying a drug affinity complex (DAC), a reactive linker that binds albumin and greatly prolongs circulation. The form described here lacks that linker. Human studies of the DAC version exist but are few; published work on the form without DAC is thinner still, and much of what is said about it is inferred from the parent hormone.

Kisspeptin

Kisspeptin-10 is a ten-residue peptide amide, the shortest active member of the kisspeptin family encoded by the KISS1 gene. The gene's 145-residue precursor is processed into kisspeptins of 54, 14, 13 and 10 amino acids, which all share the same C-terminal ten residues ending in Arg-Phe-NH2. Research interest in its reproductive role grew after human genetic studies linked loss of kisspeptin receptor function to a failure to enter puberty. It has since been examined in cell and animal models of hypothalamic reproductive control, and in short human physiological studies that measured gonadotropin release. Longer-term human data are limited.

How CJC-1295 (without DAC) acts

Like native GHRH, the peptide has been reported to bind the GHRH receptor, a class B G protein-coupled receptor on somatotroph cells of the anterior pituitary. Receptor activation couples to Gs, raising intracellular cAMP and releasing stored growth hormone; circulating growth hormone in turn drives IGF-1 production, mainly in the liver. The substitutions, D-alanine at position 2, glutamine at 8, alanine at 15 and leucine at 27, were chosen to resist cleavage by dipeptidyl peptidase-4 and to reduce deamidation and oxidation at vulnerable residues. Without the albumin-binding linker its half-life is short, and pharmacokinetic data specific to this form are sparse.

How Kisspeptin acts

Kisspeptin-10 has been reported to bind KISS1R, also called GPR54, a G protein-coupled receptor that signals mainly through Gq/11, phospholipase C and intracellular calcium. KISS1R is expressed on gonadotropin-releasing hormone (GnRH) neurons, and kisspeptin signalling is regarded as a principal upstream input controlling their activity. In animal and human physiological studies, exposure has been followed by GnRH release and, downstream, secretion of LH and to a lesser degree FSH from the anterior pituitary. Continuous exposure has been reported in some models to desensitise the receptor, a phenomenon that is itself a topic of study.

The records side by side

• Type: CJC-1295 (without DAC), GHRH analog (Modified GRF 1-29); Kisspeptin, Decapeptide (KISS1-derived)
• Length: CJC-1295 (without DAC), not recorded; Kisspeptin, 10 amino acids
• Molecular weight: CJC-1295 (without DAC), 3647.2 g/mol; Kisspeptin, 1302.4 g/mol
• Molecular formula: CJC-1295 (without DAC), C165H269N47O46; Kisspeptin, C63H83N17O14

Reading a comparison

A comparison places two records side by side; it does not merge them. Each description above is drawn from that compound's own record, and the two were not necessarily characterised by the same methods, at the same time, or to the same level of detail. Before comparing any attribute, it is worth establishing that both records describe the substance you think they describe — names are not identifiers, and two entries sharing a name can differ in salt form, stereochemistry or the convention used to state a mass. Where a figure carries no method beside it, the comparison is between two reported numbers rather than between two measurements.