Metal clips induce folding of a short unstructured peptide into an alpha-helix via turn conformations in water. Kinetic versus thermodynamic products

Short peptides corresponding to two to four alpha-helical turns of proteins are not thermodynamically stable helices in water. Unstructured octapeptide Ac-His1-Ala2-Ala3-His4-His5-Glu6-Leu7-His8-NH(2) (1) reacts with two [Pd((15)NH(2)(CH(2))(2)(15)NH(2))(NO(3))(2)] in water to form a kinetically stable intermediate, [[Pden](2)[(1,4)(5,8)-peptide]](2), in which two 19-membered metallocyclic rings stabilize two peptide turns. Slow subsequent folding to a thermodynamically more stable two-turn alpha-helix drives the equilibrium to [[Pden](2)[(1,5)(4,8)-peptide]] (3), featuring two 22-membered rings. This transformation from unstructured peptide via turns to an alpha-helix suggests that metal clips might be useful probes for investigating peptide folding.     

An Interactive Computer Model of University Room Usage

An interactive computer model of room usage in a university was designed and constructed in order to study limitations imposed on student numbers by existing accommodation, to allocate rooms efficiently to classes and to plan new buildings.     

Reactions of cisplatin hydrolytes, cis-[Pt(15NH3)2(H2O) 2]2+, with N-acetyl-L-cysteine

The reaction of cis-[Pt(¹⁵NH₃)2(H₂O) ₂] ²⁺ (3) with N-acetylcysteine [H₃accys] was investigated in aqueous solution. In this reaction, the ammine in the platinum complex formed was liberated. A mono-dentate sulfur-boundplatinum(II) product cis-[Pt(¹⁵NH₃)₂(H₂O)(H2accys-S)]⁺ (7) and six-membered che-late ring complex cis-[Pt(¹⁵NH₃)₂ (Haccys-S,O)] (8) were formed in solution. The dinuclear sulfur-bridged complex 9, giving a broad peak in ¹⁵N NMR, was also observed, but only present in very tiny amounts. The mass spectrometry (ES-MS) was undertaken from this re action, and the product detected was only the dinuclear sulfur bridged platinum species and species related to it by ammine loss.     

The influence of boundary layer growth on shock tube test times

Summary A theoretical and experimental investigation of the limitation on shock tube test times which is caused by the development of laminar and turbulent boundary layers behind the incident shock is presented. Two theoretical methods of predicting the test time have been developed. In the first a linearised solution of the unsteady one-dimensional conservation equations is obtained which describes the variations in the average flow properties external to the boundary layer. The boundary layer growth behind the shock is related to the actual extent of the hot flow and not, as in previous unsteady analyses, to its ideal extent. This new unsteady analysis is consequently not restricted to regions close to the diaphragm. Shock tube test times are determined from calculations of the perturbed shock and interface trajectories. In the second method a constant velocity shock is assumed and test times are determined by approximately satisfying only the condition of mass continuity between the shock and the interface. A critical comparison is made between this and previous theories which assume a constant velocity shock. Test times predicted by the constant shock speed theory are generally in agreement with those predicted by the unsteady theory, although the latter predicts a transient maximum test time in excess of the final asymptotic value. Shock tube test times have also been measured over a wide range of operating conditions and these measurements, supplemented by those reported elsewhere, are compared with the predictions of the theories; good agreement is generally obtained. Finally, a simple method of estimating shock tube test times is outlined, based on self similar solutions of the constant shock speed analysis.Nomenclature a speed of sound - A, B, C constants defined in section 5.3 - D shock tube diameter - K =/q ^m, boundary layer growth constant, see Appendices A and B - l hot flow length - m constant, =1/2 or 4/5 for laminar or turbulent boundary layers, respectively - M ₀ initial shock Mach number at the diaphragm - M _s shock Mach number at station x _s - M ₂ =(U ₀–u ₂)/a ₂, hot flow Mach number relative to the shock front - N = ₂ a ₂/ ₃ a ₃, the ratio of acoustic impedances across the interface - P pressure - P* =P _e–P ₂, perturbation pressure - q boundary layer growth coordinate defined in § 2 - Q =(W–1+S) K - r radial distance from shock tube axis - S boundary layer integral defined by equation A6 - t time - t =/ , dimensionless ratio of test times - T =l/l , Roshko's dimensionless ratio of hot flow lengths - u axial flow velocity in laboratory coordinate system, see figure 1a - u* =u _e–u₂, perturbation axial flow velocity - U shock velocity - U ₀ initial shock velocity at the diaphragm - U* =U–U ₀, perturbation shock velocity - v axial flow velocity in shock-fixed coordinate system, see figure 1b - w radial flow velocity - W =U ₀/(U ₀–u ₂), density ratio across the shock - x axial distance from shock tube diaphragm - x _s, x _s axial distance between shock wave and diaphragm - t = _I/ , dimensionless ratio of test times - X =l _I/l , Roshko's dimensionless ratio of hot flow lengths - y =(D/2)–r, radial distance from the shock tube wall - ratio of specific heats - boundary layer thickness; undefined - boundary layer displacement thickness - boundary layer thickness defined by equation A2 - characteristic direction defined by dx/dt = (u ₂–a ₂) - =(M ₀ ² +1)/(M ₀ ² –1) - viscosity - characteristic direction defined by dx/dt=(u ₂+a ₂) - density - * = _te–₂, perturbation density - Prandtl number - shock tube test time - =M ₀ ² /(M ₀ ² –1) Suffices 1 conditions in the undisturbed flow ahead of the shock - 2 conditions immediately behind an unattenuated shock - 3 conditions in the expanded driver gas - 4 conditions in the undisturbed driver gas - e conditions between the shock and the interface, averaged across the inviscid core flow - i conditions at the interface - I denotes the predictions of ideal shock tube theory - asymptotic conditions given when x _s and t - s conditions at or immediately behind the shock - w conditions at the shock tube wall - a, b, b ¹, c, d, d ¹, f, f ¹, g, g ¹, j, k, k ¹ conditions at the points indicated in figure 2     

Linkage isomerism in the binding of pentapeptide Ac-His(Ala)3His-NH2 to (ethylenediamine)palladium(II): effect of the binding mode on peptide conformation

The reaction of the pentapeptide Ac-His1-Ala2-Ala3-Ala4-His5-NH2 (AcHAAAHNH2) (1) with [Pd(en)(ONO2)2] (en = NH2CH2CH2NH2) in either DMF-d(7) or H2O:D2O (90%:10%) gave three linkage isomers of [Pd(en)(AcHAAAHNH2)](2+) (2), 2a, 2b, and 2c, which differ only in which pair of imidazole nitrogen atoms bind to Pd. In the most abundant isomer, 2a, Pd is bound by N1 from each of the two imidazole rings. In the minor isomers 2b and 2c, Pd is bound by N1(His1) and N3(His5) and by N3(His1) and N1(His5), respectively. The reactions of [Pd(en)(ONO2)2] with the N-methylated peptides Ac-(N3-MeHis)-Ala-Ala-Ala-(N3-MeHis)-NH2 (AcH*AAAH*NH2) (3), Ac-(N3-MeHis)-Ala-Ala-Ala-(N1-MeHis)-NH2 (AcH(*)AAAH(#)NH2) (4), and Ac-(N1-MeHis)-Ala-Ala-Ala-(N3-Me-His)-NH2 (AcH(#)AAAH(*)NH2) (5) each gave a single species [Pd(en)(peptide)](2+) in N,N-dimethylformamide (DMF) or aqueous solution, 7, 8, and 9, respectively, with Pd bound by the two nonmethylated imidazole nitrogen atoms in each case. These complexes were analogous to 2a, 2b, and 2c, respectively. Ac-(N1-MeHis)-Ala-Ala-Ala-(N1-MeHis)-NH2 (AcH(#)AAAH(#)NH2) (6) with [Pd(en)(ONO2)2] in DMF slowly gave a single product, [Pd(en)(AcH(#)AAAH(#)NH2)](2+) (10), in which Pd was bound by the N3 of each imidazole ring. The corresponding linkage isomer of 2 was not observed. Complex 10 was also the major product in aqueous solution, but other species were also present. All compounds were exhaustively characterized in solution by multinuclear 1D ((1)H , (13)C, and, with (15)N-labeled ethylenediamine, (15)N) and 2D (correlation spectroscopy, total correlation spectroscopy, transverse rotating-frame Overhauser effect spectroscopy (T-ROESY), heteronuclear multiple-bond correlation, and heteronuclear single quantum coherence) NMR spectra, circular dichroism (CD) spectra, electrospray mass spectroscopy, and reversed-phase high-performance liquid chromatography. ROESY spectra were used to calculate the structure of 2a, which contained a single turn of a peptide alpha helix in both DMF and water, the helix being better defined in DMF. The Pd(en)(2+) moiety was not used in structure calculations, but its location and coordination by one imidazole N1 from each histidine to form a 22-membered metallocycle were unambiguously established. Convergence of the structures was greatest when calculated with two hydrogen-bond constraints (Ala4 peptide NH...OC acetyl and His5 peptide NH...OC-His1) that were indicated by the low temperature dependence of these NH chemical shifts. Vicinal HN-CHalpha coupling constants and chemical shifts of alpha-H atoms were also consistent with a helical conformation. Similar long-range ROE correlations were observed for [Pd(en)(AcH(*)AAAH(*)NH2)](2+) (7), which displayed a CD spectrum in aqueous solution that suggested the presence of some helicity. Long-range ROE correlations were not observed for 8, 9, or 10, but a combination of NMR data and CD spectroscopy was interpreted in terms of the conformational behavior of the coordinated pentapeptide. Only for the linkage isomer [Pd(en)(AcH(*)AAAH(#)NH2)](2+) (8) was there evidence of a contribution from a helical conformation. The data for 8 were interpreted as interconversion between the helix and random coil conformations. Zn(2+) with peptides gave broad NMR peaks attributed to lability of this metal ion, while reactions of cis-[Pt(NH3)2(ONO2)2] were slow, giving a complex mixture of products rather than the macrochelate ring observed with Pd(en)(2+). In summary, these studies indicate that Pd(en)(2+) coordinates to histidine with similar preference for each of the two imidazole nitrogens, enabling the formation of up to four linkage isomers in its complexes with pentapeptides His-xxx-His. Only the N1-N1 linkage isomer that forms a 22-membered macrochelate ring is able to induce an alpha-helical peptide conformation, whereas the 20- and 21-membered rings of linkage isomers do not. This suggests that linkage isomeric mixtures may compromise histidine coordination to metal ions and reduce alpha-helicity.     

Synthesis and Optical Properties of Diaza‐ and Tetraazatetracenes

A series of functionalized diaza‐ and tetraazatetracenes was synthesized, either by condensation of an aromatic diamine with an ortho‐quinone/diethyloxalate followed by chlorination with POCl₃ to give diazatetracenes or by palladium‐catalyzed coupling of a phenylenediamine with various 2,3‐dichloroquinoxalines to give tetraazatetracenes (after oxidation with MnO₂). Representative examples included halogenated and nitrated derivatives. The optical properties of these azatetracenes were discussed with respect to their molecular structures and substitution patterns. The diazatetracenes and tetraazatetracenes formed two different groups that had significantly different electronic structures and properties. Furthermore, 1,2,3,4‐tetrafluoro‐6,11‐bis((triisopropylsilyl)ethynyl)benzo[b]phenazine was synthesized, which is the first reported fluorinated diazatetracene. Single‐crystal X‐ray analysis of this compound is reported.     

Alpha-turn mimetics: short peptide alpha-helices composed of cyclic metallopentapeptide modules

Alpha-Helices are key structural components of proteins and important recognition motifs in biology. Short peptides (相似文献   

Exploiting the Structural Metamorphosis of Polymers to ‘Wrap’ Micron-Sized Spherical Objects

There is growing interest in developing methods to ‘wrap’ nano- and micron-sized biological objects within films that may offer protection, enhance their stability or improve performance. We describe the successful ‘wrapping’ of lectin-decorated microspheres, which serve as appealing model micron-sized objects, within cross-linked polymer film. This approach utilizes polymer chains able to undergo a structural metamorphosis, from being intramolecularly cross-linked to intermolecularly cross-linked, a process that is triggered by polymer concentration upon the particle surface. Experiments demonstrate that both complementary molecular recognition and the dynamic covalent nature of the crosslinker are required for successful ‘wrapping’ to occur. This work is significant as it suggests that nano- and micron-sized biological objects such as virus-like particles, bacteria or mammalian cells—all of which may benefit from additional environmental protection or stabilization in emerging applications—may also be ‘wrapped’ by this approach.