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Conformational Rigidity (conformational + rigidity)
Selected AbstractsStrong Circularly Polarized Luminescence from Highly Emissive Terbium Complexes in Aqueous SolutionEUROPEAN JOURNAL OF INORGANIC CHEMISTRY, Issue 21 2010Amanda P. S. Samuel Abstract Two luminescent terbium(III) complexes have been prepared from chiral ligands containing 2-hydroxyisophthalamide (IAM) antenna chromophores and their non-polarized and circularly-polarized luminescence properties have been studied. These tetradentate ligands, which form 2:1 ligand/TbIII complexes, utilize diaminocyclohexane (cyLI) and diphenylethylenediamine (dpenLI) backbones, which we reasoned would impart conformational rigidity and result in TbIII complexes that display both large luminescence quantum yield (,) values and strong circularly polarized luminescence (CPL) activities. Both TbIII complexes are highly emissive, with , values of 0.32 (dpenLI-Tb) and 0.60 (cyLI-Tb). Luminescence lifetime measurements in H2O and D2O indicate that while cyLI-Tb exists as a single species in solution, dpenLI-Tb exists as two species: a monohydrate complex with one H2O molecule directly bound to the TbIII ion and a complex with no water molecules in the inner coordination sphere. Both cyLI-Tb and dpenLI-Tb display increased CPL activity compared to previously reported TbIII complexes made with chiral IAM ligands. The CPL measurements also provide additional confirmation of the presence of a single emissive species in solution in the case of cyLI-Tb, and multiple emissive species in the case of dpenLI-Tb. [source] Synthesis and chemical stability of a disulfide bond in a model cyclic pentapeptide: Cyclo(1,4)-Cys-Gly-Phe-Cys-Gly-OHJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 10 2006Henry T. He Abstract Many cyclic peptides are formed using a disulfide bond to increase their conformational rigidity; this provides receptor selectivity and increased potency. However, degradation of the disulfide bond in formulation can lead to a loss of structural stability and biological activity of the peptide. Therefore, the objective of this study was to study the stability of peptide 1 (cyclo(1,4)-Cys-Gly-Phe-Cys-Gly-OH). This cyclic peptide was synthesized using Boc strategy via solution-phase peptide synthesis and purified using semi-preparative HPLC. The accelerated stability studies of the cyclic peptide were conducted in buffer solutions at pH 1.0,11.0 with controlled ionic strengths at 70°C. The pH-rate profile shows that the peptide has an optimal stability around pH 3.0 with a V-shape between pH 1.0 and 5.0. Two small plateaus are observed at pH 5.0,7.0 and pH 8.0,10.0, indicating hydrolysis on different ionized forms of the cyclic peptide. One product was observed at acidic pH due to peptide bond hydrolysis at Gly2-Phe3. The number of degradation products increases as the pH increases from neutral to basic, and most of the degradation products at neutral and basic pH are derived from the degradation at the disulfide bond. © 2006 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 95:2222,2234, 2006 [source] Analysis of the factors that stabilize a designed two-stranded antiparallel ,-sheetPROTEIN SCIENCE, Issue 6 2002Juan F. Espinosa Abstract Autonomously folding ,-hairpins (two-strand antiparallel ,-sheets) have become increasingly valuable tools for probing the forces that control peptide and protein conformational preferences. We examine the effects of variations in sequence and solvent on the stability of a previously designed 12-residue peptide (1). This peptide adopts a ,-hairpin conformation containing a two-residue loop (D-Pro-Gly) and a four-residue interstrand sidechain cluster that is observed in the natural protein GB1. We show that the conformational propensity of the loop segment plays an important role in ,-hairpin stability by comparing 1 with DP, N mutant 2. In addition, we show that the sidechain cluster contributes both to conformational stability and to folding cooperativity by comparing 1 with mutant 3, in which two of the four cluster residues have been changed to serine. Thermodynamic analysis suggests that the high loop-forming propensity of the DPG segment decreases the entropic cost of ,-hairpin formation relative to the more flexible NG segment, but that the conformational rigidity of DPG may prevent optimal contacts between the sidechains of the GB1-derived cluster. The enthalpic favorability of folding in these designed ,-hairpins suggests that they are excellent scaffolds for studying the fundamental mechanisms by which amino acid sidechains interact with one another in folded proteins. [source] An improved tripod amphiphile for membrane protein solubilizationPROTEIN SCIENCE, Issue 12 2000Seungju M. Yu Abstract Intrinsic membrane proteins represent a large fraction of the proteins produced by living organisms and perform many crucial functions. Structural and functional characterization of membrane proteins generally requires that they be extracted from the native lipid bilayer and solubilized with a small synthetic amphiphile, for example, a detergent. We describe the development of a small molecule with a distinctive amphiphilic architecture, a "tripod amphiphile," that solubilizes both bacteriorhodopsin (BR) and bovine rhodopsin (Rho). The polar portion of this amphiphile contains an amide and an amine-oxide; small variations in this polar segment are found to have profound effects on protein solubilization properties. The optimal tripod amphiphile extracts both BR and Rho from the native membrane environments and maintains each protein in a monomeric native-like form for several weeks after delipidation. Tripod amphiphiles are designed to display greater conformational rigidity than conventional detergents, with the long-range goal of promoting membrane protein crystallization. The results reported here represent an important step toward that ultimate goal. [source] Multiple crystal forms of the cell-wall invertase inhibitor from tobacco support high conformational rigidity over a broad pH rangeACTA CRYSTALLOGRAPHICA SECTION D, Issue 6 2006Michael Hothorn Plant acid invertases catalyse the breakdown of sucrose. Their activity is tightly regulated through interaction with specific protein inhibitors. The complex between the cell-wall invertase inhibitor Nt-CIF and its target enzyme is stable only at acidic pH, as found in the plant cell wall. Since the pH in this compartment can be modulated between pH 4 and 6 in planta, the rapid dissociation of the inhibitor,enzyme complex at neutral pH may represent a regulatory event. Here, it is analyzed whether the inhibitory component undergoes structural rearrangements upon changes in the pH environment. Six crystal forms grown at pH 4.6,9.5 and diffracting up to 1.63,Å indicate only small structural changes in CIF. This suggests that complex dissociation at neutral pH is mediated either by rearrangements in the enzyme or by a complex pattern of surface charges in the inhibitor,enzyme binding interface. [source] | ||||||||||