Synthesis, Structural Characterization, and Bioactivity of the Stable Peptide RCB-1 from Ricinus communis.
The Ricinus communis biomarker peptides RCB-1 to -3 comprise homologous sequences of 19 (RCB-1) or 18 (RCB-2 and -3) amino acid residues. They all include four cysteine moieties, which form two disulfide bonds. However, neither the 3D structure nor the biological activity of any of these peptides is known. The synthesis of RCB-1, using microwave-assisted, Fmoc-based solid-phase peptide synthesis, and a method for its oxidative folding are reported. The tertiary structure of RCB-1, subsequently established using solution-state NMR, reveals a twisted loop fold with antiparallel β-sheets reinforced by the two disulfide bonds. Moreover, RCB-1 was tested for antibacterial, antifungal, and cytotoxic activity, as well as in a serum stability assay, in which it proved to be remarkably stable.
Division of Pharmacognosy, Department of Medicinal Chemistry, Uppsala University, Biomedical Centre , Box 574, SE-751 23 Uppsala, Sweden.|School of Engineering and Applied Sciences, National University of Mongolia , Ulaanbaatar-46, Mongolia.
Delgerbat
D
Boldbaatar
Division of Pharmacognosy, Department of Medicinal Chemistry, Uppsala University, Biomedical Centre , Box 574, SE-751 23 Uppsala, Sweden.
Sunithi
S
Gunasekera
Division of Pharmacognosy, Department of Medicinal Chemistry, Uppsala University, Biomedical Centre , Box 574, SE-751 23 Uppsala, Sweden.|Department of Chemistry, Faculty of Science, University of Malaya , 50603 Kuala Lumpur, Malaysia.
Hesham R
HR
El-Seedi
Division of Pharmacognosy, Department of Medicinal Chemistry, Uppsala University, Biomedical Centre , Box 574, SE-751 23 Uppsala, Sweden.
Ulf
U
Göransson
D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D000935:Antifungal Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D001232:Aspergillus fumigatus / Q000187:drug effects; D002176:Candida albicans / Q000187:drug effects; D003545:Cysteine / Q000737:chemistry; D004534:Egypt; D004926:Escherichia coli / Q000187:drug effects; D006801:Humans; D008826:Microbial Sensitivity Tests; D008872:Microwaves; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D010940:Plant Proteins / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D012278:Ricinus / Q000737:chemistry*; D012639:Seeds / Q000737:chemistry; D013211:Staphylococcus aureus / Q000187:drug effects
D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D010446:Peptide Fragments; D010940:Plant Proteins; C000605743:RCB-1 peptide, Ricinus communis; D003545:Cysteine