Structural analysis of peptide fragments has provided useful information on the secondary structure of integral membrane proteins built from a helical bundle (up to seven transmembrane segments). Comparison of those results to recent X-ray crystallographic results showed agreement between the structures of the fragments and the structures of the intact proteins. Lactose permease of Escherichia coli (lac Y) offers an opportunity to test that hypothesis on a substantially larger integral membrane protein. Lac Y contains a bundle of 12 transmembrane segments connected by 11 loops. Eleven segments, each corresponding to one of the loops in this protein, were studied. Five of these segments form defined structures in solution as determined by multidimensional nuclear magnetic resonance. Four peptides form turns, and one peptide reveals the end of one of the transmembrane helices. These results suggest that some loops in helical bundles are stabilized by short-range interactions, particularly in smaller bundles, and such intrinsically stable loops may contribute to protein stability and influence the pathway of folding. Greater conformational flexibility may be found in large integral membrane proteins.

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Synthesis and Biological Activity of 23-Ethylidene-26-hydroxy-22-oxocholestaneDerivatives from Spirostanic Sapogenins. -Three new cholestane frameworks of type (II) are obtained by reductive cleavage of the F-ring of oxoepoxycholestane derivatives (I) without detectable competing 1,2-reduction of the α,β-unsaturated carbonyl group at C-22. This selectivity is attributed to steric hindrance around C-22, which is corroborated by the finding that Luche's reagent is unable to effect 1,2-reduction of the C-22 carbonyl of epoxycholestenes (I). Utilizing this reagent, reduction of the carbonyl group occurs to afford a diastereomeric mixture of epimeric alcohols (III) and (IV). The selectivity of this reaction is totally reversed in the absence of cesium chloride. Steroids (I), (II) and (III) display some anti-cancer activity against CEM, and (Ib) reveals cytotoxic activity against the MCF7 line as well. -(PEREZ-DIAZ, J. O. H.; RAROVA, L.; MUNOZ OCAMPO, J. P.; MAGANA-VERGARA, N. E.; FARFAN, N.; STRNAD, M.; SANTILLAN*, R.; Eur. J. Med. Chem. 51 (2012) 67-78, http://dx.