In order to understand how aromatic residues modulate the function of membrane-spanning proteins, we examined the role of the four tryptophans in gramicidin A (gA) in determining the average duration and permeability characteristics of membrane-spanning gramicidin channels; the tryptophan residues were replaced by tyrosine (gramicidin T, gT), tyrosine O-benzyl ether [gramicidin T(Bzl), gT(Bzl)], naphthylalanine (gramicidin N, gN), and phenylalanine (gramicidin M enantiomer, gM-). These analogues form channels with durations and conductances that differ some 10- and 16-fold, respectively. The single-channel conductance was invariably decreased by the Trp----Yyy replacement, and the relative conductance alterations were similar in phosphatidylcholine (DPhPC) and monoglyceride (GMO) bilayers. The duration variations exhibited a more complex pattern, which was quite different in the two membrane environments: in DPhPC bilayers, gN channels have an average duration that is approximately 2-fold longer than that of gA channels; in GMO bilayers, the average duration of gN channels is about one-tenth that of gA channels. The sequence-dependent alterations in channel function do not result from alterations in the channels' peptide backbone structure, because heterodimers can form between the different analogues and gramicidine A, and there is no energetic cost associated with heterodimer formation [cf. Durkin, J. T., Koeppe, R. E., II, & Andersen, O. S. (1990) J. Mol. Biol. 211, 221]. The alterations in permeability properties are consistent with the notion that Trp residues alter the energy profile for ion permeation through long-range electrostatic interactions.
Exchange of benzylidene ligand of commercially available Grubbs catalysts 1a or 1b with an appropriate soluble-polymer supported ligand leads to new boomerang type catalysts either of the Grubbs (3) or the Hoveyda type (4a or 4b). These catalysts, supported on poly-(ethylene glycol) (PEG), were fully characterized by solution NMR and MALDI mass spectrometry. They were tested in ring-closing metathesis (RCM), and 1 H NMR analysis provided key information concerning the recovery of the catalyst at the end of the reaction. While in the case of 3 the active ruthenium did not hook back to the ligand, catalysts 4a and 4b can be recovered and recycled. 4b owning a N-heterocyclic carbene ligand is particularly active and was used in the parallel synthesis of cyclic amino esters.
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