The solution ~tructure of sarafoloxln .(~b in water has been determined ufing high.resolution NM R spcctr0s¢opy, 12"/proton=prolon diflance mea~. urements and three ~ dihedral an~le conltraint~ derived from NMR spectra were used to calculate the solution structure t,~lnll =t con~hination of distance geometry and restrained molecular dynamic=¢. The major structural feature of the resulting family of five structures was a right.her, tied =.helix extending from K9 to QI?. In contrast, the C.terminal region of the pcptkle appears not to adopt a preferred conformation in aqueous solution, The present atructure i =~ compared with those previottslydetcrmined for endothelin peptides In non.aqueou~ solvents,

The aqueous solution structure of the 21-residue vasoactive peptide hormone endothelin-3 has been determined using high-resolution NMR spectroscopy. A total of 177 proton-proton distance measurements and 5 chi 1 dihedral angle constraints derived from NMR spectra were used to calculate the structure using a combination of distance geometry and dynamical simulated annealing calculations. The calculations reveal a highly ordered, compact conformation in which a helical region extending from K9 to C15 lies in close apposition with the C-terminal hexapeptide; this interaction seems to be largely driven by hydrophobic interactions. Structure-activity studies are interpreted in terms of the conformational features of the calculated endothelin-3 structure.

Studies of the causes of ageing are often obscured by the complexity of this phenomenon, hindering investigations in this area. In particular, the variable characteristics of ageing complicate analysis at a molecular level. It is proposed that to gain insight into ageing, the problem must first be simplified by restricting studies to an aspect of the ageing processes. It is suggested that progeria, which presents a less complicated etiology and phenotype than other accelerated ageing diseases, allows research to focus on a regulation site involved in development and ageing.

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