Abstract
Marine derived cyclo(Gly-l-Ser-l-Pro-l-Glu) was selected as a lead to evaluate antitumor-antibiotic activity. Histidine was chosen to replace the serine residue to form cyclo(Gly-l-His-l-Pro-l-Glu). Cyclic tetrapeptides (CtetPs) were then synthesized using a solution phase method, and subjected to antitumor and antibiotic assays. The benzyl group protected CtetPs derivatives, showed better activity against antibiotic-resistant Staphylococcus aureus in the range of 60–120 μM. Benzyl group protected CtetPs 3 and 4, exhibited antitumor activity against several cell lines at a concentration of 80–108 μM. However, shortening the size of the ring to the cyclic tripeptide (CtriP) scaffold, cyclo(Gly-l-Ser-l-Pro), cyclo(Ser-l-Pro-l-Glu) and their analogues showed no antibiotic or antitumor activity. This phenomenon can be explained from their backbone structures.
Highlights
The discovery and study of antimicrobial peptides (AMPs) has greatly affected the field of drug design [1,2]
We focused our efforts using Cyclic tetrapeptides (CtetPs) as β-turn (U-anticancer peptides (ACPs)) mimicry as innate defense regulators (IDRs) to explore novel antitumor activities
The antibacterial and antitumor activities of analogue peptides based on cyclic tetramer and trimer were described
Summary
The discovery and study of antimicrobial peptides (AMPs) has greatly affected the field of drug design [1,2]. Cyclic tetrapeptides (CtetPs) are constrained by privileged secondary structures, can self-assemble, and stack up to form hollow, β-sheet-like nanotubes [19] They have been characterized as potent and highly selective molecules in a diverse range of therapeutic areas such as the antiproliferative agent cyclo(L-Pro-L-Leu-L-Pro-L-Leu) [20], tyrosinase inhibitor cyclo(L-Pro-L-Tyr-L-Pro-L-Val) [21], and many histone deacetylase inhibitors [22,23,24]. Several analogs based on the target cyclo(Gly-L-Ser-L-Pro-L-Glu) were synthesized Their antibiotic and antitumor activities were evaluated with minimal inhibitory concentrations (MICs) assay [34] and MTT assay [35]
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