Template-constrained somatostatin analogues: a biphenyl linker induces a type-V' turn.
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Biomedical subjects
Publications and source records attributed to R P Cheng.
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The discovery of a discretely folded homotrimeric betabetaalpha motif (BBAT1) was recently reported (J. Am. Chem. Soc. 2001, 123, 1002-1003). Herein the design, synthesis, and analysis of a small library of peptides which led to the isolation of BBAT1 is described. betabetaalpha peptides based on the monomeric sequence of BBA5 (Folding Des. 1998, 120, 95-103) were synthesized to include the anthranilic acid/nitrotyrosine fluorescence quenching pair to rapidly detect interpeptide association. In the first generation of peptides synthesized, truncations in the loop region connecting the beta-hairpin to the alpha-helix revealed that a two-residue deletion in the loop promoted an interpeptide association as detected by fluorescence quenching. An additional library of 22 loop-truncated betabetaalpha peptides was subsequently synthesized to include a variety of sequence mutations in an effort to enhance the observed peptide-peptide binding. From the fluorescence quenching screen, peptide B2 was found to possess the strongest fluorescence-quenching response, indicative of a strong peptide-peptide association. Due the poor solubility of peptide B2, the S-methylated cysteine at position 9 in the loop was substituted with a glycine to generate peptide BBAT1 which possessed greatly improved water solubility and formed discrete trimers. The successful design of this oligomeric betabetaalpha structure will likely aid the design of more complex alpha-beta superstructures and further our understanding of the factors controlling protein-protein interactions at alpha-beta protein interfaces.
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Small proteins or protein domains generally require disulfide bridges or metal sites for their stabilization. Here it is shown that the beta beta alpha architecture of zinc fingers can be reproduced in a 23-residue polypeptide in the absence of metal ions. The sequence was obtained through an iterative design process. A key feature of the final design is the incorporation of a type II' beta turn to aid in beta-hairpin formation. Nuclear magnetic resonance analysis reveals that the alpha helix and beta hairpin are held together by a defined hydrophobic core. The availability of this structural template has implications for the development of functional polypeptides.
This article reports on the result of an investigation on the prevalence of liver alveolar echinococcosis (LAE) and liver cystic echinococcosis (LCE) in the peasants and the residents of Xiji County, Ningxia Hui Autonomous Region. Among 2,389 selected persons examined with B-ultrasound, 197 cases were diagnosed to have LAE or LCE; the prevalence being 8.2%. Of the 197 cases, 141 (5.9%) had LAE; 56 (2.3%) had LCE. Among 1,413 peasants, 9.7% had LAE; 3.8% had LCE. Among 976 residents, 0.4% had LAE, 0.2% had LCE. Obviously, the peasants were more prone to be infected with the disease, suggesting LAE had much to do with the job of hunting the fox and capturing the Citellus dauricus, while the infectious source of LCE was mainly the domestic dog.