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Publication Abstract from PubMed

Unnatural oligomers that can mimic protein surfaces offer a potentially useful strategy for blocking biomedically important protein-protein interactions. Here we evaluate an approach based on combining alpha- and beta-amino acid residues in the context of a polypeptide sequence from the HIV protein gp41, which represents an excellent testbed because of the wealth of available structural and biological information. We show that alpha/beta-peptides can mimic structural and functional properties of a critical gp41 subunit. Physical studies in solution, crystallographic data, and results from cell-fusion and virus-infectivity assays collectively indicate that the gp41-mimetic alpha/beta-peptides effectively block HIV-cell fusion via a mechanism comparable to that of gp41-derived alpha-peptides. An optimized alpha/beta-peptide is far less susceptible to proteolytic degradation than is an analogous alpha-peptide. Our findings show how a two-stage design approach, in which sequence-based alpha-->beta replacements are followed by site-specific backbone rigidification, can lead to physical and biological mimicry of a natural biorecognition process.

Structural and biological mimicry of protein surface recognition by {alpha}/{beta}-peptide foldamers.,Horne WS, Johnson LM, Ketas TJ, Klasse PJ, Lu M, Moore JP, Gellman SH Proc Natl Acad Sci U S A. 2009 Aug 17. PMID:19706443^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.