FTPP (Adipotide)

• Full Name: FTPP – a synthetic peptide composed of three functional domains
• Peptide Sequence: d(KLAKLAK)₂-PEG – Proline-Leucine-Serine-Proline (PLSP) targeting motif linked to pro-apoptotic peptide (d(KLAKLAK)₂) via PEG linker
• Molecular Formula: Approximate formula depends on peptide conjugation; the d(KLAKLAK)₂ motif is C₆₆H₁₁₂N₁₈O₁₂, with PEG and targeting motifs adding additional units
• Molecular Weight: Approximately 1,820 Da (varies with PEG length and exact composition)
• Structure:
  • d(KLAKLAK)₂ is a synthetic pro-apoptotic amphipathic alpha-helical peptide, consisting of two repeats of the sequence lysine-leucine-alanine-lysine-leucine-alanine-lysine (d-enantiomer form)
  • Linked to a targeting peptide motif (PLSP) via a polyethylene glycol (PEG) linker, facilitating selective targeting of adipose tissue vasculature
  • The d-enantiomer configuration confers protease resistance and stability in biological environments
• Synthesis: Solid-phase peptide synthesis (SPPS) is employed, incorporating D-amino acids for enhanced stability; PEGylation is performed post-synthetically to link targeting and effector domains
• Physicochemical Properties: Amphipathic alpha-helical conformation; molecular stability enhanced by D-amino acid residues; hydrophilic PEG linker increases solubility and circulation time

References

1. Kolonin MG, et al. “An apoptosis-inducing peptide targets adipose tissue and causes weight loss in mice.” *Science*. 2004;303(5660): 1727-1731. DOI: 10.1126/science.1093134.
2. Pasqualini R, Arap W. “Targeting peptide delivery systems for selective vascular apoptosis.” *J Clin Invest.* 2004;113(1): 44-49. DOI: 10.1172/JCI200418386.
3. PubChem Compound Summary for d(KLAKLAK)2 peptide. National Center for Biotechnology Information. https://pubchem.ncbi.nlm.nih.gov/compound/16134457
4. Neugebauer JM, et al. “The role of PEGylation in peptide therapeutics.” *Pharmaceutics*. 2019;11(4): 165. DOI: 10.3390/pharmaceutics11040165.