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Synthetic Molecules Hint at Usefulness Against HIV

Last Updated: August 20, 2009.

Synthetic peptide-like molecules called "foldamers" demonstrated an ability to prevent HIV from infecting host cells while maintaining resistance to enzyme degradation, according to research published online Aug. 17 in the Proceedings of the National Academy of Sciences.

THURSDAY, Aug. 20 (HealthDay News) -- Synthetic peptide-like molecules called "foldamers" demonstrated an ability to prevent HIV from infecting host cells while maintaining resistance to enzyme degradation, according to research published online Aug. 17 in the Proceedings of the National Academy of Sciences.

W. Seth Horne, Ph.D., of the University of Wisconsin in Madison, and colleagues discuss their development of α/β-peptides that mimic the functional and structural characteristics of the HIV gp41 protein.

The researchers found that the gp41-mimetic α/β-peptides can block fusion between cells and HIV using a mechanism that is similar to that in gp41-derived α-peptides. However, α/β-peptides may be less sensitive to proteolytic degradation than an analogous α-peptide; such degradation is a major drawback to the clinical use of α-peptide drugs.

"The present work demonstrates the value of designing unnatural oligomers that can 'read' the sophisticated recognition signals that have been evolutionarily encoded in natural proteins. Potent inhibition of HIV infectivity by α/β-peptides represents an important advance in the development of functional foldamers, but many challenges remain," the authors write. "For example, the successful examples of sequence-based backbone modification reported to date have involved mimicry of helical structures; it will be interesting to see whether this approach can be applied to longer and more complex prototype sequences with defined tertiary folds."

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