Design and synthesis of anti-cancer cyclopeptides containing triazole skeleton

Abstract

We describe the design and synthesis of some hypothetical heptapeptides specifically to overcome the neoplastic activity of ras oncogene and their anti-cancer activities were studied. To improve the anti-cancer activity of the synthesized peptides, their structure modifications were done based on a sequential Ugi/Huisgen 1,3-Dipolar cyclization reaction. The cyclopeptides which contained triazole skeleton showed significant anti-cancer activity against cancer cells with mutated ras oncogene such as A549, PC3 and C26 cells. This study clearly shows the importance of triazole skeleton in biological activity of the peptides. It might be possible to overcome the difficulties involved in making complex peptides by employing this elegant chemistry.

Tuning the anticancer activity of a novel pro-apoptotic peptide using gold nanoparticle platforms

“…AntiCP web server was used to predict the anticancer efficacy of the given sequence so that it could meet the purposes of the present study 52 . The peptide synthesis and its conjugation with LA are described in supplementary data 53 54 . After purification of peptide conjugate by semi-preparative RP-HPLC, the purity of the lyophilized peptide was examined by analytical high-performance liquid chromatography (HPLC, Purity >95%).…”

Cyclisation To Form Small, Medium and Large Rings by Use of Catalysed and Uncatalysed Azide–Alkyne Cycloadditions (AACs)

“…Recently, Tahoori and colleagues developed a set of triazole‐containing cyclic heptapeptides, designed to overcome the neoplastic activity of the ras oncogene . The authors tested four peptide sequences for their anticancer activities against A549 human lung cancer cells in vitro.…”

“…Recently, Tahoori and colleagues developed a set of triazolecontaining cyclic heptapeptides, designed to overcome the neoplastic activity of the ras oncogene. [57] The authors tested four peptide sequences for their anticancer activities against A549 human lung cancer cells in vitro. The structure of the most active of these four sequences -the proline-rich sequence H-SAPPPRK-OH -was then further elaborated to allow its synthesis through an isocyanide-based multicomponent reaction (IMCR) and head-to-tail cyclisation.…”

Synthesis of novel cyclopeptides containing heterocyclic skeletons

“…The type of reagents used for each sequence depends on various parameters, such as the size of the ring. 13,14 Other methods of ring formation require the use of different chemical reactions, such as the creation of lactam bridges; 15 disulde bridges, which are most commonly used for sequences with two cysteine amino acids; 16,17 click chemistry; 18,19 metathesis; 20,21 and the Ugi, 22,23 Hantszch, 24,25 Horner-Wadsworth-Emmons (HWE), 26 Mannich 27 and Heck 28 reactions.…”

“…8,30 However, in this review, we decided to investigate the insertion of heterocycle rings in cyclopeptides. Heterocycles, which are an extensively published subject, include triazole, 18 imidazole, 31-33,37 oxazole 25, [33][34][35] and thiazole rings. 13,24,25,34,36 These rings endow peptide structures with rigidity, and the interactions of these structures with receptors can be studied more readily and accurately ( Fig.…”