Karle, Isabella L and Das, Chittaranjan and Balaram, Padmanabhan (2000) De novo protein design: Crystallographic characterization of a synthetic peptide containing independent helical and hairpin domains. In: Proceedings of the National Academy of Sciences of the United States of America, 97 (7). pp. 3034-3037.
The Meccano (or Lego) set approach to synthetic protein design envisages covalent assembly of prefabricated units of peptide secondary structure. Stereochemical control over peptide folding is achieved by incorporation of conformationally constrained residues like alpha-aminoisobutyric acid (Aib) or DPro that nucleate helical and beta-hairpin structures, respectively. The generation of a synthetic sequence containing both a helix and a hairpin is achieved in the peptide BH17, Boc-Val-Ala-Leu-Aib-Val-Ala-Leu-Gly-Gly-Leu-Phe-Val-DPro-Gly-Leu-Phe-Val-OMe (where Boc is t-butoxycarbonyl), as demonstrated by a crystal structure determination. The achiral -Gly-Gly- linker permits helix termination as a Schellman motif and extension to the strand segment of the hairpin. Structure parameters for C89H143N17O20z2H2O are space group P21, a = 14.935(7) Å, b = 18.949(6) Å, c = 19.231(8) Å, beta = 101.79(4)°, Z = 2, agreement factor R1 5 8.50% for 4,862 observed reflections >4s(F), and resolution of '0.98 Å.
|Item Type:||Journal Article|
|Department/Centre:||Division of Biological Sciences > Molecular Biophysics Unit|
|Date Deposited:||27 Aug 2004|
|Last Modified:||19 Sep 2010 04:14|
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