Helical Conformations of Hexapeptides Containing N-Terminus Diproline Segments

The role of N-terminus diproline segments in facilitating helical folding in short peptides has been investigated in a set of model hexapeptides of the type Piv-Xxx-Yyy-Aib-Leu-Aib-Phe-OMe (Piv, pivaloyl). Nine sequences have been investigated with the following N-terminus dipeptide segments: (D)Pro-Ala (4) and Pro-Psi Pro (5, Psi, pseudoproline), Ala-Ala (6), Ala-Pro (7), Pro-Ala (8), Aib-Ala (9), Ala-Aib (10). The analog sequences Piv-Pro-Pro-Ala-Leu-Aib-Phe-OMe (2) and Piv-Pro-Pro-Ala-Aib-Ala-Aib-OMe (3) have also been studied. Solid state conformations have been determined by X-ray crystallography for peptides 4, 6, and 8 and compared with the previously determined crystal structure of peptide 1 (Boc-Pro-Pro-Aib-Leu-Aib-Val-OMe); (Rai et al., JACS 2006, 128, 7916-7928). Peptides 1 and 6 adopt almost identical helical conformations with unfolding of the helix at the N-terminus Pro (1) residue. Peptide 4 reveals the anticipated (D)Pro-Ala type II' beta-turn, followed by a stretch of 3(10)-helix. Peptide 8 adopts a folded conformation stabilized by four successive 4 -> 1 intramolecular hydrogen bonds. Ala (2) adopts an alpha(L) conformation, resulting in a type II beta-turn conformation followed by a stretch of 3(10)-helix. Conformational properties in solution were probed using solvent perturbation of NH chemical shifts which permit delineation of hydrogen bonded NH groups and nuclear Overhauser effects (NOEs) between backbone protons, which are diagnostic of local residue conformations. The results suggest that continuous helical conformations are indeed significantly populated for peptides 2 and 3. Comparison of the results for peptides 1 and 2, suggest that there is a significant influence of the residue that follows diproline segments in influencing backbone folding. (C) 2010 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 94: 360-370, 2010

Rice husk SiO2 (NPs) supported-BO3H3: a highly active, solvent-free and recyclable catalyst to dihydropyrimidin-2(1H)ones-(thiones) and coumarin-3-carboxylic acid synthesis

3,4-Dihydropyrimidin-2(1H)ones(thiones) (DHPM) and coumarin-3-carboxylic acid are obtained in excellent to good yield by employing green catalyst under solvent-free condition. The condensation of substituted arylaldehyde, 1,3-diketoester and urea/thiourea in the presence of green catalyst after 1 h of stirring at 50 degrees C resulted in DHPM. The reaction of substituted o-hydroxybenzaldehyde with Meldrum's acid in the presence of catalyst under sonication for a few minutes gave coumarin-3-carboxylic acid. Here, we have used Lewis acid catalyst RHA-SiO2(NPs)-BO3H3 derived from the agro-waste of rice husk, a heterogeneous catalyst for important organic scaffold synthesis. The reaction required low catalyst loading (1.2 mg) to achieve a target product under solvent-free condition. A series of other derivatives of heterogeneous catalysts synthesized are RHA-SiO2, RHA-SiO2(NPs), RHA-SiO2-BO3H3. We examined their catalytic activity in the synthesis of DHPM and coumarin-3-carboxylic acid. Only the reaction catalysed by RHA-SiO2(NPs)-BO3H3 gave excellent yield of the product. The final isolated pure product has been fully characterized by various spectroscopic methods and confirmed

Solid-state NMR at natural isotopic abundance for the determination of conformational polymorphism - the case of designed beta-turn peptides containing di-prolines

The proton double quantum-carbon single quantum correlation experiment has been applied to designed peptides in the solid state in natural isotopic abundance. Analogous to nOe studies in solution, through-space double-quantum connectivities have been exploited to obtain the cis-trans conformational polymorphism of diproline residues occurring at beta-turns in the peptides