Conformations strain differences

A different approach toward cyclic peptides has been presented by Leatherbarrow and coworkers, employing ring-dosing metathesis (RCM) on a solid support [50], The authors reported on the synthesis of conformationally strained cyclic peptides of the Bowman-Birk inhibitor type, which are naturally occurring serine protease... 

Tanaka, M., Chien, P., Naber, N., Cooke, R., and Weissman,J. S. (2004). Conformational variations in an infectious protein determine prion strain differences. Nature 428, 323-328. 

A hard-to-understand aspect of the "protein-only" theory of prion diseases is the existence of various "strains" of prion proteins. These do not involve differences in amino acid sequence but differences in the conformations of the PrPSc forms and in the glycosylation patterns. dmw How can there be several different conformations of the same protein, all of which seed the conversion of normal PrP into differing insoluble forms In spite of this puzzle, support for the explanation of strain differences comes from a yeast prion system, which involves transcription termination factor eRF3.x z In this system, which involves a prion whose insoluble form can be redissolved by guanidine hydrochloride,aa differing strains have also been described.ybb cc Nevertheless, the presence of the various strains of animal prions, as well as observed vaccination of inbred mice against specific strains,dd may be more readily understood if the disease is transmitted by an unidentified virus rather than by a pure protein.1/U ee/ff In fact, the diseases have not been successfully transmitted by truly virus-free proteins synthesized from recombinant DNA.ee... 

Human carbonic anhydrase 11 X-ray analyses were combined with in-depth conformationai anaiyses using ab initio calculations to clarify the origin of the large variations in potency observed with different optical isomers of thienothiopyran-2-sulfonamide derivatives. Modifications ieading to enhanced affinity via the reduction of conformational strain were identified. 43, 178... 

Another factor besides PrP conformations in strain differences could be differences in PrP /PrP interaction surfaces, as with the models for species barriers discussed previously. For example, Warwicker (1997b) has interpreted his heterodimer model in light of residues important in determining strain differences. In particular, in this case, he focused on conserved and nonpolar residues and proposed that there are two distinct patches on the molecule that can interact with membrane or with a neighboring protein. This hypothesis leads to two different membrane-attached PrP orientations, or faces, that would be presented to an incoming PrP molecule. In a more recent study, Warwicker (1999) discusses how charge interactions between PrP and the membrane may affect scrapie formation. Along these lines, Morillas et al. 

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