Tryptophan-Containing Cyclic Decapeptides with Activity against Plant Pathogenic Bacteria

Area of Science:

• Medicinal Chemistry
• Agricultural Science
• Microbiology

Background:

• Phytopathogenic bacteria pose significant threats to crop yields and agricultural sustainability.
• Cyclic peptides are a class of compounds with diverse biological activities, including antimicrobial properties.
• Tryptophan (Trp) and Phenylalanine (Phe) are aromatic amino acids that can influence peptide structure and function.

Purpose of the Study:

• To synthesize and evaluate a library of 66 cyclic decapeptides containing tryptophan (Trp) for antibacterial activity.
• To assess the hemolytic activity of these Trp-containing peptides.
• To compare the antibacterial efficacy of Trp analogues with previously reported Phe analogues against specific plant pathogens.

Main Methods:

• Solid-phase synthesis of 66 cyclic decapeptides incorporating a Trp residue.
• Screening of synthesized peptides against three key phytopathogenic bacteria: *Pseudomonas syringae* pv. *syringae*, *Xanthomonas axonopodis* pv. *vesicatoria*, and *Erwinia amylovora*.
• Determination of minimum inhibitory concentrations (MIC) and evaluation of hemolytic activity.

Main Results:

• The incorporation of Trp significantly improved antibacterial activity compared to Phe analogues, with 40-46 Trp analogues showing lower MIC values.
• Specific Trp-containing peptides demonstrated potent activity: 26 peptides against *X. axonopodis* pv. *vesicatoria* (MIC 0.8–3.1 μM), 21 against *P. syringae* pv. *syringae* (MIC 1.6–6.2 μM), and six against *E. amylovora* (MIC 6.2–12.5 μM).
• Trp derivatives generally exhibited comparable or lower hemolytic activity than Phe analogues, with 49 peptides showing ≤ 20% hemolysis at 125 μM. Peptides BPC086W and BPC108W showed excellent profiles (MIC 0.8–12.5 μM, hemolysis ≤ 8% at 125 μM).

Conclusions:

• Tryptophan-containing cyclic decapeptides represent a promising class of compounds for combating phytopathogenic bacteria.
• The synthesized Trp analogues exhibit potent antibacterial activity with acceptable safety profiles regarding hemolysis.
• Selected peptides, such as BPC086W and BPC108W, are strong candidates for further development as novel agents for plant protection.