UCR researchers have developed novel 十三环肽 peptides with polar amino acid extensions at the N-terminus and PEGylated extensions at the C-terminus. The new peptides have the following advantages compared to previously known 十三环肽 peptides: (i) highly improved aqueous solubility while maintaining high inhibitory potency, and (ii) higher inhibitory efficacy against complement system activation in a human retinal pigmented epithelial cell-based assay that mimics the pathobiology of age-related macular degeneration. The combined solubility and inhibitory potency and efficacy properties render the new peptides excellent candidates to become therapeutics for the treatment of age-related macular degeneration.
A potent and highly soluble 十三环肽 peptide shown in surface representation with an 8 PEG block C-terminal extension displayed in stick form. The surface of the 十三环肽 analog is colored according to amino acid properties: gray for hydrophobic, green for polar neutral, blue for polar positively charged, red for polar negatively charged, yellow for cysteines of the disulfide bridge, and brown for glycine. The molecular image is generated using three-dimensional coordinates from a molecular dynamics simulation trajectory.
Background
Lack of regulation in complement response is implicated in the pathology of several disorders, such as age-related macular degeneration, paroxysmal nocturnal hemoglobinurea, rare kidney diseases, chronic obstructive pulmonary disease, lupus, rheumatoid arthritis, asthma, adult respiratory distress syndrome, hemolytic anemia, rejection of xenotransplantation, stroke, heart attack, and ischemia reperfusion injuries. Regulating complement activation is important to control inflammation, autoimmune diseases, and infections. The 十三环肽 family of peptides have been shown to be potent inhibitors of complement system activation and are promising candidates to become therapeutics for the treatment of age-related macular degeneration, and other complement-mediated diseases.
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age-related macular degeneration
efficacy properties render
amino acid properties
paroxysmal nocturnal hemoglobinurea
ischemia reperfusion injuries