Crystallization of Human Aquaglyceroporins for Neutron Diffraction Studies.

Aquaglyceroporins are channels that facilitate the flux of glycerol and water across lipid bilayers. Although structural information is available for several aquaglyceroporins, the details of how water and glycerol selectivity are maintained and how protons are excluded remain elusive. An approach to obtaining data on the hydrogen atom positions is to apply neutron macromolecular crystallography.

Synthesis of cyclic peptide analogues of the 3(10) helical Pro138-Gly144 segment of human aquaporin-4 by olefin metathesis.

Four cyclic pentapeptides and two cyclic heptapeptides modelled on the 3(10) helical Pro138-Gly144 segment of the water channel aquaporin-4 (AQP4) postulated to mediate adhesive interactions between AQP4 tetramers were synthesised by olefin metathesis. Three related acyclic pentapeptides Boc-Ser(All)-Xaa1-Val-Ser(All)-Gly-OMe (Xaa1 = Val, Aib; Boc = tert-butoxycarbonyl; All = allyl) and Boc-Ser(Bn)-Val-Val-Gly-Gly-OMe (Bn = benzyl) and two acyclic heptapeptides Boc-Pro-Pro-Ser(All)-Val-Val-Ser(All)-Gly-OMe and Boc-Pro-Pro-Ser(Bn)-Val-Val-Gly-Gly-OMe were also prepared. NMR, CD and IR data provided evidence that the peptides can access a 3(10) helical structure in apolar solvents and pointed to a significant stabilising effect of the olefinic bridge on helicity in an aqueous environment.