Kisspeptin Peptide Powder for Research- High Purity Synthetic Kisspeptin-10/-54

In recent neuroendocrine research, freeze-dried kisspeptin powders, mainly the decapeptide kisspeptin-10 (KP-10) and the 54-residue precursor peptide kisspeptin-54 (KP-54), have served as standard materials for elucidating the central regulation of reproduction, pubertal maturation, and metastasis suppression. If they are produced by rigorous solid-phase synthesis that is completed by preparative reversed-phase liquid chromatography and counter-ion exchange desalting, then both KP-10 and KP-54 have a C-terminal RF-amide motif that is critical for the potent activation of the corresponding G protein-coupled receptor, also known as KISS1R, GPR54, or AXOR12. The former (KP-10) causes a rapid, pulse-like activation of gonadotrophin-releasing hormone (GnRH) systems, while the latter (KP-54) acts as a sustained, slow-release agonist depot that is resistant to aminopeptidase degradation. The difference is often used to better understand pulsatile versus surge release of hypothalamic signals, to generate predictable animal models of early or late puberty, and to further elucidate the role of kisspeptin as a metastasis suppressor in carcinomas of reproductive organs. In recent lots, accompanying residual solvent certificates, endotoxin measurements, and mass-spectrometric analyses are provided so that the high quality of these peptides meets the critical standards of reproducibility required for peer-reviewed publication.

Overview of Kisspeptin Peptides

The kisspeptins were discovered as products of proteolytic processing from a 145-amino acid precursor that is translated from the KISS1 gene. Cleavage at sites between clusters of basic amino acids releases multiple, amidated, biologically active peptides of 10 to 54 amino acids that have a conserved C-terminal decapeptide sequence. This sequence utilizes a type-I β-turn recognized by the transmembrane domain of the receptor. This leads to Gαq/11 activation of phospholipase C, causing calcium release from intracellular stores, and phosphorylation of extracellular-signal-regulated kinase (ERK). As the receptor is highly expressed on soma, dendrites and presynaptic terminals of GnRH neurons, nanomolar concentrations of kisspeptin can drive a dose-dependent secretion of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) from the anterior pituitary gland. The receptor is not subject to desensitization by transient receptor activation. However, after chronic exposure, kisspeptin-KISS1R interaction leads to rapid receptor internalization in a β-arrestin dependent manner. This has provided the basis for the use of either bolus injections or continuous infusions when utilizing kisspeptin in an experimental paradigm. KISS1R has also been identified in the placental trophoblast, ovarian theca cells, spermatogonial stem cells and a subset of ERα-positive breast epithelial cells, making it an ideal target for probing the potential autocrine or paracrine effects of KISS1R signaling on cell proliferation, angiogenesis and metastatic quiescence.

Fig. 1 Kisspeptin and the hypothalamic/pituitary/gonadal (HPG) axis.^1,5

Molecular Features and Variants (Kisspeptin-10/-54)

The minimum bioactive core, kisspeptin-10, forms a nascent type-I β-turn that orients the aromatic side chains of tryptophan-3 and phenylalanine-6 into a hydrophobic pocket between trans-membrane helices III and VI of KISS1R. The C-terminal arginine has a delocalized positive charge that forms a bidentate salt bridge to the conserved aspartate 7.49 of the receptor, a contact lost by non-amidation that accounts for the > 100-fold loss in potency of the free-acid derivative. Oxidation of the N-terminal tyrosine to 3,4-dihydroxyphenylalanine occurs readily in copper-rich media, generating a catechol motif that undergoes reversible cyclisation with the neighboring asparagine amide, producing a bicyclic lactam whose receptor efficacy is halved; this artefact is often mis-assigned as "degradation" in stability reports unless monitored by high-resolution mass spectrometry. In contrast, Kisspeptin-54 is a metastable foldamer: residues 11–32 form an amphipathic α-helix with a marked lysine-rich polar face that mediates heparan-sulphate binding at the cell surface, which functionally creates a two-dimensional reservoir that buffers extracellular concentration spikes. A second helical segment (residues 38–50) is interrupted by a Gly-Pro-Asn hinge that confers conformational flexibility; small-angle X-ray scattering suggests that the molecule switches between extended and hairpin conformers with a persistence length of ≈ 2.5 nm. Such plasticity slows enzymatic attack because the scissile bonds are transiently buried within the hydrophobic core. Moreover, the hinge region contains a sulfation consensus (Tyr21-Xaa-Xaa-Gly) that is recognized by Golgi-resident tyrosyl-protein sulfotransferase-2; sulfation increases net negative charge, enhances heparin affinity and extends half-life in placental explants by ~ 60 %. The two helices also permit homodimerization through leucine-zipper-like interactions. This concentration-dependent effect can be detected by analytical ultracentrifugation when studying the peptides at concentrations > 15 µM. Dimerization does not abrogate receptor activation, but rather changes the downstream signalling bias of the activated receptor: the monomer preferentially recruits Gαq, whereas the dimer recruits β-arrestin-2 to change the transcriptome from immediate-early genes (c-fos, Egr-1) towards long-term synaptic plasticity markers (Homer1a, Narp). Experimentalists that modulate the in vivo dose should be aware that seemingly linear concentration–response curves may in fact mask a hidden phase-transition that is governed by peptide self-assembly, rather than receptor occupancy.

Lab-Grade Quality Standards

In addition to traditional RP-HPLC, kisspeptin is purified by HILIC to separate glyco- and sulfoforms which co-elute on an alkyl-bonded stationary phase. As these post-translational variants have identical activity but different metabolism, their unintentional co-enrichment may confound in vivo results, so they are separated to the baseline on a zwitterionic sulfoalkylbetaine column with an acetonitrile gradient in 10 mM ammonium acetate pH 4.7. For endotoxin removal, anion-exchange membrane adsorbers functionalized with grafted polyethyleneimine ligands are used, as lipopolysaccharide binds to these at ionic strengths at which the cationic peptide is free to pass; after washing with 0.5 M NaOH to regenerate the matrix, this yields endotoxin < 0.03 EU/mg, a level required for intrathecal injection. Residual trifluoroethanol, N,N-dimethylformamide and triisopropylsilane are measured by static head-space GC-MS; acceptance criteria are 50 ppm, 100 ppm and 30 ppm respectively in accordance with ICH Q3C. To confirm the absence of microbial spores, the final bulk solution is passed through a 0.2 µm filter (PES membranes pre-treated with 20 % ethanol to remove surfactant residues that would otherwise leach plasticizers into the peptide stream). Each batch is stress-tested by accelerated stability (40 °C / 75 % RH) over six months; release criteria are < 1 % oxidation, < 0.5 % deamidation and no detectable backbone cleavage (by tandem MS). In parallel, microbiological monitoring is performed with regular bioburden testing on the system and kinetic chromogenic endotoxin assay, both samples taken every 30 min during fill–finish. Finally, a certified reference material (CRM) is prepared by quantitative amino-acid analysis after vapour-phase hydrolysis, and is used to calibrate in-house HPLC response factors in order to control lot-to-lot consistency without external dependence.

Research Applications

Synthetic kisspeptin-10 and kisspeptin-54 are now broadly used as reagent tools in reproductive biology and oncology research: to recapitulate and rescue known patterns of GnRH release from the hypothalamus in animal models, to control or time ovulation in livestock and assisted-conception programs, and to study the antitumorigenic pathways that suppress EMT, angiogenesis and metastatic colonization in placenta-, breast- and ovary-derived cancers.

Fertility Studies & GnRH Stimulation

Kisspeptin peptides are increasingly being used as positive controls to study the hypothalamic pulse generator. As in vivo administration of single boluses of kisspeptin-10 by ICV injection in rodents results in a rapid and dose-dependent LH pulse which reaches a peak within 15 min and returns to baseline within 1 h (which phenocopies the physiologic neural code initiating ovulation), such administration mimics the ovulatory signal in its natural form. By contrast, the mean LH level is chronically raised and maintains measurable pulse frequency when kisspeptin-54 is administered subcutaneously by osmotic mini-pumps and has been used in the clinic to rescue delayed puberty in kiss1-deficient mice and to synchronize oestrus in agricultural settings. In addition to the central route of administration, kisspeptin also can be delivered intranasally. The latter route has the advantage of being non-invasive, and is thought to access KISS1R-expressing neurones in the medial preoptic area by olfactory-trigeminal afferents. This protocol has been performed in both sheep and non-human primate models. Ex vivo, using acute brain slices, kisspeptin elicits a biphasic membrane potential change in GnRH neurons that begins with a transient depolarization that is TRPC-like cation channel dependent, which is then followed by a sustained plateau which is mediated by chloride efflux through NKCC1. This electrical activity can then be used as a pharmacodynamic biomarker when testing newer analogues. Recently, it has been shown that environmentally-induced epigenetic changes to the kisspeptin promoter are heritable; thus, a controlled administration of kisspeptin can also be used to understand how early-life exposure to endocrine disruptors affects adult fertility.

Fig. 2 The distribution of kisspeptin in central and peripheral areas and its role in reproduction.^2,5

Cancer and Reproductive System Research

In addition to its role in neuroendocrine pathways, KISS1 was first described as a metastasis suppressor gene, and its expression inversely correlates with the progression of several cancers, including melanoma, breast, ovarian and endometrial cancers. Treatment of triple negative breast cancer MDA-MB-231 spheroids with recombinant kisspeptin-10 inhibited their chemotactic invasion of Matrigel, in a KISS1R-dependent manner, through decreased NF-κB nuclear translocation and concomitant down-regulation of matrix metalloproteinase-9. In the ovary, autocrine kisspeptin signalling negatively regulates luteal angiogenesis through suppression of VEGF-A secretion by theca-endothelial co-cultures; similarly, xenografts were less vascularized when kiss1-over-expressing granulosa cells were transplanted into immune-deficient mice. Choriocarcinoma placental cancer lines treated with kisspeptin-54 undergo cell-cycle arrest at G2/M, with increased p21Cip1 and hypo-phosphorylated retinoblastoma protein. In contrast to this cytostatic effect, prolonged treatment with kisspeptin does not activate apoptosis, making it a good target for cytostatic cancer adjuvants that aim to preserve function while keeping tumors dormant. KISS1R is the target of current nanoparticle-conjugated kisspeptin cancer research for improved targeted delivery, as well as dual-agonist constructs that target both KISS1R and ERα.

Technical Specifications

Due to the reproducibility requirements for neuroendocrine and tumor-related research, our kisspeptin-10 and ‑54 for research use are synthesized by Fmoc solid-phase techniques. The included certificate of analysis (CoA) includes information about mass error, counter-ion content, and stress-related stability data. By storing the lyophilized peptides under the suggested conditions, as well as by following the provided instructions, undesired oxidation and deamidation, as well as surface adsorption losses, can be minimized. Under these conditions, the peptide batches produced are expected to be uniform in their target receptor-specific bioactivity in both in vitro and in vivo experiments.

Explore Our Kisspeptin Peptides & Custom Synthesis Options

At Creative Peptides, we supply high-purity Kisspeptin-10 and Kisspeptin-54 peptides designed exclusively for research use. All peptides are manufactured under strict quality standards, with verified purity and stability testing. Whether you need small quantities for pilot studies or bulk supply for long-term projects, we can deliver reliable peptides with global shipping.

For specialized requirements, our custom peptide synthesis service allows you to order Kisspeptin variants tailored to your protocols-ensuring flexibility, reproducibility, and lab-grade performance.

Take your research further with premium Kisspeptin peptides trusted by scientists worldwide. Contact us today to request a quote, inquire about bulk pricing, or discuss your custom synthesis needs. Our dedicated team will ensure you receive the highest-quality peptides with fast, secure delivery to your lab.

Kisspeptin Peptides We Provides

Frequently Asked Questions (FAQs)

1. Can I order Kisspeptin in bulk quantities?

Yes. We offer bulk supply options at competitive pricing for laboratories and institutions conducting large-scale or long-term studies.

2. Do you provide custom synthesis services?

Absolutely. We can customize peptide length, modifications, or formulations according to your research protocols. Contact us to discuss your project requirements.