Enhancing the Stability of Tumor Homing LyP-1 Peptide Using Cyclization and Retro Grafting Strategies

Kara Ş., AYAZOĞLU DEMİR E., ÇELİK UZUNER S., Akcan M.

International Journal of Peptide Research and Therapeutics, cilt.29, sa.2, 2023 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 29 Sayı: 2
  • Basım Tarihi: 2023
  • Doi Numarası: 10.1007/s10989-023-10504-7
  • Dergi Adı: International Journal of Peptide Research and Therapeutics
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, EMBASE, Veterinary Science Database
  • Anahtar Kelimeler: LyP-1, Peptide design, Cyclization, Grafting, Retro sequence, Peptide stability, TRYPSIN-INHIBITOR SFTI-1, IN-VITRO EVALUATION, CYCLIC-PEPTIDES, ANTICANCER PEPTIDE, SUNFLOWER SEEDS, DESIGN, ANALOGS, ANTAGONIST, BRADYKININ, CYCLOTIDE
  • Karadeniz Teknik Üniversitesi Adresli: Evet

Özet

Anticancer peptide therapeutics are promising candidates for cancer treatment as they are highly specific to their targets and can have tumor-homing abilities. Several studies have been shown that a nine-residue tumor-homing LyP-1 peptide can be used in anticancer agent development and in tumor imaging studies. However, because it is a small linear peptide, it is very unstable in serum as most of the peptide therapeutics face before they enter to clinical studies. The main aim of this study is to enhance the serum stability of LyP-1 using cyclization and grafting (and/or retro grafting) strategies. Four grafted versions onto sunflower trypsin inhibitor peptide SFTI-1 and a cyclic homodimerized version of LyP-1 were synthesized and tested on MDA-MB-435S cancer (melanoma) cells and HFF-1 normal fibroblast cells in comparison with cisplatin chemotherapeutics. The cyclic homodimer LyP-1 peptide exhibited extraordinary stability in serum. Additionally, the retro grafted peptides have also improved stability that indicates the retro sequence concept provides peptides with higher stability.