Details

Autor(en) / Beteiligte

• Horne, W. Seth
• Johnson, Lisa M
• Ketas, Thomas J
• Klasse, Per Johan
• Lu, Min
• Moore, John P
• Gellman, Samuel H

Titel

Structural and biological mimicry of protein surface recognition by α/β-peptide foldamers

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2009-09, Vol.106 (35), p.14751-14756

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2009

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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 α- and β-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 α/β-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 α/β-peptides effectively block HIV-cell fusion via a mechanism comparable to that of gp41-derived α-peptides. An optimized α/β-peptide is far less susceptible to proteolytic degradation than is an analogous α-peptide. Our findings show how a two-stage design approach, in which sequence-based α[rightward arrow]β replacements are followed by site-specific backbone rigidification, can lead to physical and biological mimicry of a natural biorecognition process.