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High-resolution structural characterization of a helical alpha/beta-peptide foldamer bound to the anti-apoptotic protein Bcl-xL.

ABSTRACT: Get into the groove: The first high-resolution structure of a foldamer bound to a protein target is described (see picture; foldamer in sticks). The foldamer consists of alpha- and beta-amino acid residues and is bound to the anti-apoptotic protein Bcl-x(L). The overall binding mode and key interactions observed in the foldamer/Bcl-x(L) complex mimic those seen in complexes of Bcl-x(L) with natural alpha-peptide ligands. Additional contacts in the foldamer/Bcl-x(L) complex involving beta-amino acid residues appear to contribute to binding affinity.

SUBMITTER: Lee EF

PROVIDER: S-EPMC2843084 | biostudies-literature | 2009

REPOSITORIES: biostudies-literature

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High-resolution structural characterization of a helical alpha/beta-peptide foldamer bound to the anti-apoptotic protein Bcl-xL.

Lee Erinna F EF Sadowsky Jack D JD Smith Brian J BJ Czabotar Peter E PE Peterson-Kaufman Kimberly J KJ Colman Peter M PM Gellman Samuel H SH Fairlie W Douglas WD

Angewandte Chemie (International ed. in English) 20090101 24

Get into the groove: The first high-resolution structure of a foldamer bound to a protein target is described (see picture; foldamer in sticks). The foldamer consists of alpha- and beta-amino acid residues and is bound to the anti-apoptotic protein Bcl-x(L). The overall binding mode and key interactions observed in the foldamer/Bcl-x(L) complex mimic those seen in complexes of Bcl-x(L) with natural alpha-peptide ligands. Additional contacts in the foldamer/Bcl-x(L) complex involving beta-amino a ...[more]

PMID: 19229915

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