Metabolic
A synthetic peptidomimetic studied for selective targeting of white adipose tissue vasculature.
Adipotide is a synthetic peptidomimetic investigated for its ability to home to blood vessels in white adipose tissue. Researchers examine it in preclinical models to study its binding to adipose endothelium and the apoptotic processes observed in those cells. It consists of a vascular-homing segment (CKGGRAKDC) linked to a proapoptotic helical domain (D(KLAKLAK)₂), designed to associate with a receptor on adipose tissue blood vessels.
Last reviewed · For research use only.
Type
Synthetic peptide (peptidomimetic)
Molecular formula
C₁₁₁H₂₀₆N₃₆O₂₈S₂
Molecular weight
2557.2 g/mol
CAS number
859216-15-2
Amino acids
26
Sequence
CKGGRAKDC-GG-D(KLAKLAK)₂
Modification
Contains two D-enantiomeric (D-amino acid) heptapeptide repeats forming an amphipathic proapoptotic domain; cysteine residues present in the homing motif; linear conjugate connected by a GG linker.
Adipotide is a ligand-directed vascular-targeting peptidomimetic. The CKGGRAKDC homing segment binds to prohibitin (PHB), a protein enriched on the surface of endothelial cells in white adipose tissue. Biochemical studies have examined whether this sequence mimics an internal loop of annexin A2 (ANXA2), a PHB-associated protein co-expressed on adipose endothelial surfaces. The conjugated D(KLAKLAK)₂ proapoptotic domain is a membrane-disrupting helical peptide that, upon internalization, engages mitochondrial membranes and is studied for its role in initiating endothelial cell apoptosis. Separate research has examined the formation of a PHB–ANXA2–CD36 complex and its potential contribution to fatty acid transport at the adipose endothelium.
Research Focus
Studied in preclinical metabolic-research models and in vitro systems examining adipose tissue vasculature, endothelial apoptosis, and prohibitin/annexin A2 receptor biology.
The Adipotide concept originated from in vivo phage display experiments designed to identify peptide sequences that selectively home to blood vessels of white adipose tissue. Kolonin et al. (2004) screened phage libraries in a rodent metabolic model and isolated the CKGGRAKDC homing motif, identifying prohibitin (PHB) — a protein found on adipose endothelial cell surfaces — as its binding partner. The conjugate CKGGRAKDC-GG-D(KLAKLAK)₂ was assembled by linking this homing motif to a proapoptotic helical domain and studied for its vascular-targeting properties in the adipose context. Staquicini et al. (2011) applied combinatorial vascular receptor mapping to examine receptor expression — including PHB and annexin A2 — in human white adipose tissue.
Kim et al. (2010) studied Adipotide in diet-induced rodent models over a multi-week administration period. The study monitored metabolic and neuroendocrine parameters across the study period. The research examined relationships between adipose vascular targeting and systemic signaling in the rodent metabolic-research model context.
Barnhart et al. (2011) examined Adipotide in a non-human-primate metabolic model in a 4-week dose-ranging study. Investigators tracked biodistribution and changes in adipose tissue parameters using adipose imaging, examining whether adipose vascular targeting and biodistribution behavior observed in rodent models is present in primate physiology. These non-human primate studies were carried out to develop the translational research context for the compound.
Salameh et al. (2016) investigated the PHB–annexin A2 (ANXA2) interaction at the adipose endothelial surface using in vitro and ex vivo models. The study examined co-expression of PHB and ANXA2 on white adipose tissue endothelial cells, and characterised the assembly of a PHB–ANXA2–CD36 complex in the context of fatty acid exposure, examining whether the complex plays a role in transendothelial lipid handling. Knockout mouse models lacking ANXA2 were studied to examine the pathway's contribution to adipose lipid handling. Separately, phage peptide sequence analysis examined alignment of the CKGGRAKDC motif with regions of ANXA2, providing structural context for the PHB-targeting interaction.
A Phase I open-label trial (NCT01262664) examined pharmacokinetic and safety parameters of Adipotide; cited for study-design context. Detailed published data from this trial are not yet available.
Lyophilized
Store dry at −20 °C or below, protected from moisture and light.
Reconstituted
Dissolve in sterile water or dilute acetic acid
keep at 4 °C for short-term use; divide into aliquots prior to freezing and store at −80 °C.
Aliquot to avoid repeated freeze-thaw cycles; protect from light and heat.
Reviews
Daquinag A.C., Zhang Y., Kolonin M.G. (2011). Trends Pharmacol Sci — Review of vascular targeting approaches in white adipose tissue in preclinical metabolic research
Ande S.R., Nguyen K.H., Nyomba B.L.G., Mishra S. (2016). Trends Endocrinol Metab — Review of prohibitin biology in adipose tissue and immune cell contexts
Sibuyi N.R.S., Meyer M., Onani M.O., Skepu A., Madiehe A.M. (2018). Int J Nanomedicine — Review of prohibitin-targeted nanocarrier strategies in preclinical adipose vascular research
Reviews
Xu Y.X.Z., Bassi G., Mishra S. (2019). Biol Sex Differ — Review of prohibitin as a candidate effector in sex-differentiated metabolic and adipose tissue studies
Fang Y., Kaszuba T., Imoukhuede P.I. (2020). Front Physiol — Systems biology review of VEGF:VEGFR signaling in adipose vascular targeting research contexts
Cao Y. (2010). Nat Rev Drug Discov — Review of adipose tissue angiogenesis as a research target in metabolic-disease models
Clinical
ClinicalTrials.gov (2012). ClinicalTrials.gov — Phase I open-label clinical study (NCT01262664); cited for study-design context
Primary research
Salameh A., Daquinag A.C., Staquicini D.I., An Z., Hajjar K.A., Pasqualini R., Arap W., Kolonin M.G. (2016). JCI Insight — In vitro and ex vivo study of PHB–annexin A2 interaction and fatty acid transport in white adipose endothelium
Staquicini F.I., Cardó-Vila M., Kolonin M.G., Treplev M., et al. (2011). PNAS — Combinatorial vascular receptor mapping examining prohibitin and annexin A2 expression in human white adipose tissue
Barnhart K.F., Christianson D.R., Wetterau L., Erickson J.A., et al. (2011). Sci Transl Med — Dose-ranging study of Adipotide in a non-human primate metabolic-research model examining biodistribution and adipose tissue parameters
Kim D.-H., Woods S.C., Seeley R.J. (2010). Diabetes — Study of Adipotide in a diet-induced rodent metabolic-research model monitoring metabolic and neuroendocrine parameters
Kolonin M.G., Saha P.K., Chan L., Pasqualini R., Arap W. (2004). Nat Med — Phage display identification of the CKGGRAKDC adipose-vascular homing motif and prohibitin as its receptor
Kim D.-H., Sartor M.A., Bain J.R., Sandoval D., et al. (2012). Diabetes — Rodent model study examining glucose tolerance following adipose endothelium-targeted proapoptotic peptide administration
Daquinag A.C., Tseng C., Salameh A., Zhang Y., et al. (2015). Cell Death Differ — Mouse model study of targeted white adipocyte progenitor depletion using a hunter-killer peptide approach
Daquinag A.C., Tseng C., Zhang Y., Amaya-Manzanares F., et al. (2016). Mol Ther — In vivo tumor model study examining targeted proapoptotic peptides directed at adipose stromal cells
Gao Z., Daquinag A.C., Yu Y., Kolonin M.G. (2022). Diabetes — Mouse endothelial-specific PHB1 knockout model examining fatty acid transport in adipose tissue
Hossen M.N., Kajimoto K., Akita H., Hyodo M., Harashima H. (2012). J Control Release — In vivo mouse study of prohibitin-targeted nanoparticle delivery to adipose vasculature
Bacher S., Achatz G., Schmitz M.L., Lamers M.C. (2002). Biochimie — Biochemical characterisation of prohibitin–annexin A2 protein complex interactions in vitro
Bahmani T., Sharifzadeh S., Tamaddon G., et al. (2021). J Biomed Phys Eng — In vitro cell line study examining D(KLAKLAK)2 mitochondrial peptide apoptotic activity in combination with ionizing radiation
Su F., Ahn S., Saha A., DiGiovanni J., Kolonin M.G. (2019). Oncogene — Mouse tumor model study of adipose stromal cell-targeted proapoptotic peptide effects on prostate cancer progression
Research Use Only
These products are intended for research purposes only and are not for human consumption. Not FDA approved. Not intended to diagnose, treat, cure, or prevent any disease.
| Compound | Type | Molecular weight | CAS number |
|---|---|---|---|
| AdipotideThis page | Synthetic peptide (peptidomimetic) | 2557.2 g/mol | 859216-15-2 |
| GLP-3 (RT) | Synthetic peptide (acylated, 39 residues) | ~4,731 Da | 2381089-83-2 |
| GLP-1 (SM) | Synthetic peptide (acylated, 31 residues) | ~4,114 g/mol | 910463-68-2 |
| GLP-1 (TRZ) | Synthetic linear peptide (dual GLP-1R/GIPR agonist; acylated, 39 residues) | ~4,814 g/mol | 2023788-19-2 |
| AOD-9604 | Synthetic peptide (cyclic, 16 residues) | ~1,815 g/mol | 221231-10-3 |
Comparison of laboratory reference specifications only. For research use only; not a therapeutic comparison.
