Backbone Segments Research Articles

Entropically Mediated Polyolefin Blend Segregation at Buried Sapphire and Air Interfaces Investigated by Infrared−Visible Sum Frequency Generation Vibrational Spectroscopy

The segregation behavior of binary polymer blends at hydrophilic solid sapphire and air interfaces was investigated by infrared-visible sum frequency generation (SFG) vibrational spectroscopy. SFG spectra were collected from a bulk miscible blend consisting of identical molecular weight (approximately 54,000) and similar surface free energy (29-35 dyn/cm) components of atactic polypropylene (aPP) and aspecific poly(ethylene-co-propylene) rubber (aEPR). Characteristic CH resonances of the blend were contrasted with those of the individual components at both buried (sapphire/polymer) and free (air/polymer) interfaces. Preferential segregation of the aPP component was observed after annealing at both air/polymer and sapphire/polymer interfaces. SFG spectra revealed ordering of the polymer backbone segments with the methylene (CH2) groups perpendicular to the surface at the sapphire interface and the methyl (CH3) groups upright at the air interface. The SFG results indicate that the surface composition can be determined from the peak intensities that are characteristic of each component and that conformational entropy played a likely role in surface segregation. aPP occupied a smaller free volume at the surface because of a statistically smaller segment length (aPP is more flexible and has a shorter length). In addition, the high density of the ordered CH3 side branches enhanced the surface activity by allowing the long-chain backbone segments of aPP to order at the surface.

Optical and electrochemical properties of copoly(aryl ether)s consisting of alternate 2,5‐distyrylbenzene and electron‐transporting oxadiazole or triazole derivatives

AbstractNew copoly(aryl ether) P1 consisting of alternate electron‐transporting 2‐(3‐(trifluoromethyl)phenyl)‐5‐(4‐(5‐(3‐(trifluoromethyl)phenyl)‐1,3,4‐oxadiazol‐2‐yl)‐2,5‐bis(hexyloxy)phenyl)‐1,3,4‐oxadiazole and hole‐transporting 2,5‐distyrylbenzene (DSB) was synthesized via nucleophilic substitution polymerization. We investigated the optical and electrochemical properties of alternate copoly(aryl ether)s P1–P6, which contain the same hole‐transporting DSB segments, but with different electron transporting segments. The effect of trifluoromethyl groups in electron transporting segments is also discussed. Referencing to the spectra of their model compounds M1–M4, the emissions of P1–P3 are dominated exclusively by the hole‐transporting fluorophores with longer emissive wavelength about 452–453 nm via efficient excitation energy transfer. Furthermore, P1–P3 also exhibit unique variations in energy transfer in acidic media and solvatochromism in organic solvents. The highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) energy levels of P1–P4, estimated from electrochemical data, are −5.12, −5.15, −5.18, −5.00 eV and −2.93, −3.39, −3.49, −2.76 eV, respectively. The electron and hole affinity of P1–P6 can be enhanced simultaneously by introducing isolated hole‐ and electron‐transporting segments in backbone. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 5083–5096, 2005

Structural Allostery and Binding of the Transferrin·Receptor Complex

The structural allostery and binding interface for the human serum transferrin (Tf)*transferrin receptor (TfR) complex were identified using radiolytic footprinting and mass spectrometry. We have determined previously that the transferrin C-lobe binds to the receptor helical domain. In this study we examined the binding interactions of full-length transferrin with receptor and compared these data with a model of the complex derived from cryoelectron microscopy (cryo-EM) reconstructions (Cheng, Y., Zak, O., Aisen, P., Harrison, S. C. & Walz, T. (2004) Structure of the human transferrin receptor.transferrin complex. Cell 116, 565-576). The footprinting results provide the following novel conclusions. First, we report characteristic oxidations of acidic residues in the C-lobe of native Tf and basic residues in the helical domain of TfR that were suppressed as a function of complex formation; this confirms ionic interactions between these protein segments as predicted by cryo-EM data and demonstrates a novel method for detecting ion pair interactions in the formation of macromolecular complexes. Second, the specific side-chain interactions between the C-lobe and N-lobe of transferrin and the corresponding interactions sites on the transferrin receptor predicted from cryo-EM were confirmed in solution. Last, the footprinting data revealed allosteric movements of the iron binding C- and N-lobes of Tf that sequester iron as a function of complex formation; these structural changes promote tighter binding of the metal ion and facilitate efficient ion transport during endocytosis.

Isolation and Characterization of Novel Cyclotides from Viola hederaceae: SOLUTION STRUCTURE AND ANTI-HIV ACTIVITY OF vhl-1, A LEAF-SPECIFIC EXPRESSED CYCLOTIDE

Based on a newly established sequencing strategy featured by its efficiency, simplicity, and easy manipulation, the sequences of four novel cyclotides (macrocyclic knotted proteins) isolated from an Australian plant Viola hederaceae were determined. The three-dimensional solution structure of V. hederaceae leaf cyclotide-1 (vhl-1), a leaf-specific expressed 31-residue cyclotide, has been determined using two-dimensional (1)H NMR spectroscopy. vhl-1 adopts a compact and well defined structure including a distorted triple-stranded beta-sheet, a short 3(10) helical segment and several turns. It is stabilized by three disulfide bonds, which, together with backbone segments, form a cyclic cystine knot motif. The three-disulfide bonds are almost completely buried into the protein core, and the six cysteines contribute only 3.8% to the molecular surface. A pH titration experiment revealed that the folding of vhl-1 shows little pH dependence and allowed the pK(a) of 3.0 for Glu(3) and approximately 5.0 for Glu(14) to be determined. Met(7) was found to be oxidized in the native form, consistent with the fact that its side chain protrudes into the solvent, occupying 7.5% of the molecular surface. vhl-1 shows anti-HIV activity with an EC(50) value of 0.87 microm.

Branch-Point Motion in Asymmetric Star Polymers

Linear viscoelastic behavior of a series of 1,4-polyisoprene asymmetric star polymers was investigated experimentally and theoretically in order to determine how branch point motion affects terminal relaxation dynamics. For the systems studied, the branch point is connected to a moderately entangled short arm (MB/Me= 7) and two longer arms with varying numbers of entanglements (MA/Me = 7−43). The measured loss modulus manifests a clear transition from starlike to linear-like dynamics as the molecular asymmetry increases. We show that this behavior can be predicted using a tube-model for branched molecules (Frischknecht et al. Macromolecules 2002, 35, 4801) with a self-consistently determined branch-point diffusivity, Dbp = (pa0)2/2τa,B. Here a0 is the effective bare tube diameter, τa,B is the arm retraction time, and p2 = 1/[(2NAR)b2/a02] is an effective drag produced by unrelaxed backbone segments. We also compare relaxation moduli predicted by the tube model with experimental data and find good agreement over a range of short- and long-arm entanglement densities.

Viscoelastic Relaxation and Molecular Mobility of Hyperbranched Poly(ε-caprolactone)s in Their Melt State

The dynamic viscoelastic relaxation behavior and the molecular mobility of a series of hyperbranched poly(ε-caprolactone)s (HPCLs) possessing molecular architectural variation and their linear counterpart, linear poly(ε-caprolactone) (LPCL), were characterized and evaluated in conjunction with their specific molecular architectures which are the different lengths of the linear backbone segments and the different relative degrees of branching (DBs). The relative DBs, determined by the branching ratio values, were in decreasing order of HPCL-5 > HPCL-10 > HPCL-20. Dynamic viscoelastic relaxation measurements exhibited unentangled behavior for HPCLs compared to the apparently entangled linear, and the parallel G‘(ω) and G‘‘(ω) curves were observed for the HPCLs, while the LPCL exhibited a typical curve. The melt dynamics of HPCLs was observed to be complex. This characteristic dynamic behavior of HPCLs, particularly incorporating the shorter segments, can be seen to be another example of gellike power-law relaxation of hyperbranched systems. The correlation time, τc, was determined from the G‘‘(ω) and the empirical Havriliak−Negami (HN) equation, which provided a unique means to evaluate the molecular mobility. Further insights to the correlation times with the Arrhenius equation provided novel information about the temperature-dependence of the molecular mobility and the activation energy, Ea. The molecular mobility of three HPCLs was found to be higher than that of LPCL, and was observed to enhance with decreasing lengths of oligo(ε-caprolactone) segments and increasing relative DB.

Solid-state exchange NMR characterization of segmental dynamics in glassy poly(alkyl methacrylate)s

Slow side-group and main-chain β-relaxation dynamics in a series of glassy poly(alkyl methacrylate)s (PRMAs) with varying side-group sizes were studied by one-dimensional (1-D) centerband-only detection of exchange (CODEX) and static pure-exchange (PUREX) nuclear magnetic resonance (NMR) techniques. The13COO signal in 1-D PUREX experiments was analyzed to characterize the flips and small-angle motions of the side groups quantitatively. By comparing the13COO exchange intensities obtained from 1-D PUREX and CODEX experiments, it was possible to show that the small-angle reorientations vary between backbone segments. Analysis of the backbone13CH2 CODEX data supplied direct and quantitative information about the amplitudes of the main-chain motion, which is also reflected in the side-group reorientation due to the coupling between side group and backbone. The data obtained from both NMR exchange techniques were correlated, providing an accurate, consistent description of the backbone and side-group motion. The effects of side-group size and temperature on the fraction of flipping side groups were studied systematically by 1-D PUREX NMR. The flipping fraction at ambient temperature decreases with increasing the side-group size. It increases gradually with temperature for two PRMAs with conformationally flexible side groups, while it is constant over wide temperature ranges for poly(methyl methacrylate) and poly(cyclohexyl methacrylate).

Tissue-specific expression of head-to-tail cyclized miniproteins in Violaceae and structure determination of the root cyclotide Viola hederacea root cyclotide1.

The plant cyclotides are a family of 28 to 37 amino acid miniproteins characterized by their head-to-tail cyclized peptide backbone and six absolutely conserved Cys residues arranged in a cystine knot motif: two disulfide bonds and the connecting backbone segments form a loop that is penetrated by the third disulfide bond. This knotted disulfide arrangement, together with the cyclic peptide backbone, renders the cyclotides extremely stable against enzymatic digest as well as thermal degradation, making them interesting targets for both pharmaceutical and agrochemical applications. We have examined the expression patterns of these fascinating peptides in various Viola species (Violaceae). All tissue types examined contained complex mixtures of cyclotides, with individual profiles differing significantly. We provide evidence for at least 57 novel cyclotides present in a single Viola species (Viola hederacea). Furthermore, we have isolated one cyclotide expressed only in underground parts of V. hederacea and characterized its primary and three-dimensional structure. We propose that cyclotides constitute a new family of plant defense peptides, which might constitute an even larger and, in their biological function, more diverse family than the well-known plant defensins.

Synthesis of Well-Defined High-Density Branched Polymers Carrying Two Branch Chains in Each Repeating Unit by Coupling Reaction of Benzyl Bromide-Functionalized Polystyrenes with Polymer Anions Comprised of Two Polymer Segments

A series of high-density branched polymers have been synthesized by the coupling reaction of poly(4-(3-(4-bromomethylphenyl)propyl)styrene with polymer anion comprised of two same or different polymer chains, prepared from polystyryllithium and either polystyrene or polyisoprene with 1,1-diphenylethylene chain-end functionalization. Under certain conditions, the reaction proceeded essentially quantitatively to afford the requisite extremely high-density branched polymers carrying two branch chains in each repeating unit and having Mw values of up to 3 × 106. Furthermore, quite new graft-block copolymers with similar high-density branched architectures could also be successfully synthesized. The resulting polymers are well-defined in branched architecture and precisely controlled in chain lengths of both backbone and branch segments. It was however observed that the reaction efficiency was significantly affected by several variables such as degrees of polymerization of the backbone polymer and polymer anion and branched and chemical structures of the polymer anion. The structures of the resulting high-density branched polymers were investigated by intrinsic viscosity measurement. These polymers may possibly adopt starlike structures in toluene as evidenced by their g‘ values.

Architectural Effects of Poly(ε-caprolactone)s on the Crystallization Kinetics

A series of hyperbranched poly(ε-caprolactone)s (HPCLs) with molecular architectural variation, which refers to the different lengths of the linear backbone segments consisting of 5, 10, and 20 ε-caprolactone monomer units (thereby referred to as HPCL-5, HPCL-10, and HPCL-20, respectively) and the different numbers of branching points, were synthesized without significant variation in the molecular weights, and linear poly(ε-caprolactone) (LPCL) of the same chemical structure and similar molecular weight was used as the linear counterpart to HPCLs for comparison. The specific molecular architectures of these samples were characterized by 1H NMR end-group analyses. The nonisothermal crystallization exotherms of HPCLs and LPCL were measured by DSC and further analyzed by the modified Avrami method. Regardless of the samples, the Avrami exponents ranged from 2.4 to 3.3, indicating that the nucleation and growth mechanisms of the samples are apparently identical. On the other hand, the crystallization kinetics was found to be fairly affected by the molecular architectures. All the kinetic parameters estimated from DSC exotherms such as the initial slope, Si, and from the modified Avrami analyses such as the corrected rate constant, Kc, and crystallization half-time, t1/2, indicated that HPCLs with longer linear segments and fewer branches showed the faster crystallization, whereas LPCL exhibited intermediate crystallization rate between HPCL-10 and HPCL-20, i.e., HPCL-5 < HPCL-10 < LPCL < HPCL-20. The slower crystallization was linked with the frequent presence of heterogeneous branching points, hindering the regular chain packing, in the backbone of HPCLs with shorter linear segments. In addition, the faster crystallization of HPCL-20 compared with LPCL was attributed to the higher cooperative chain mobility in their melt state as evaluated by activation energy of flow. A number of spherulites developed during isothermal process from the melt were observed for all samples by POM, and the radial growth rates of these spherulites were evaluated to correspond well with the results of Si, Kc, and t1/2 from the nonisothermal crystallization analyses.

Equilibrium and Kinetic Folding of Rabbit Muscle Triosephosphate Isomerase by Hydrogen Exchange Mass Spectrometry

Unfolding and refolding of rabbit muscle triosephosphate isomerase (TIM), a model for (βα) 8-barrel proteins, has been studied by amide hydrogen exchange/mass spectrometry. Unfolding was studied by destabilizing the protein in guanidine hydrochloride (GdHCl) or urea, pulse-labeling with 2H 2O and analyzing the intact protein by HPLC electrospray ionization mass spectrometry. Bimodal isotope patterns were found in the mass spectra of the labeled protein, indicating two-state unfolding behavior. Refolding experiments were performed by diluting solutions of TIM unfolded in GdHCl or urea and pulse-labeling with 2H 2O at different times. Mass spectra of the intact protein labeled after one to two minutes had three envelopes of isotope peaks, indicating population of an intermediate. Kinetic modeling indicates that the stability of the folding intermediate in water is only 1.5 kcal/mol. Failure to detect the intermediate in the unfolding experiments was attributed to its low stability and the high concentrations of denaturant required for unfolding experiments. The folding status of each segment of the polypeptide backbone was determined from the deuterium levels found in peptic fragments of the labeled protein. Analysis of these spectra showed that the C-terminal half folds to form the intermediate, which then forms native TIM with folding of the N-terminal half. These results show that TIM folding fits the (4+4) model for folding of (βα) 8-barrel proteins. Results of a double-jump experiment indicate that proline isomerization does not contribute to the rate-limiting step in the folding of TIM.

A Comparison of the Self-association Behavior of the Plant Cyclotides Kalata B1 and Kalata B2 via Analytical Ultracentrifugation

The recently discovered cyclotides kalata B1 and kalata B2 are miniproteins containing a head-to-tail cyclized backbone and a cystine knot motif, in which disulfide bonds and the connecting backbone segments form a ring that is penetrated by the third disulfide bond. This arrangement renders the cyclotides extremely stable against thermal and enzymatic decay, making them a possible template onto which functionalities can be grafted. We have compared the hydrodynamic properties of two prototypic cyclotides, kalata B1 and kalata B2, using analytical ultracentrifugation techniques. Direct evidence for oligomerization of kalata B2 was shown by sedimentation velocity experiments in which a method for determining size distribution of polydisperse molecules in solution was employed. The shape of the oligomers appears to be spherical. Both sedimentation velocity and equilibrium experiments indicate that in phosphate buffer kalata B1 exists mainly as a monomer, even at millimolar concentrations. In contrast, at 1.6 mm, kalata B2 exists as an equilibrium mixture of monomer (30%), tetramer (42%), octamer (25%), and possibly a small proportion of higher oligomers. The results from the sedimentation equilibrium experiments show that this self-association is concentration dependent and reversible. We link our findings to the three-dimensional structures of both cyclotides, and propose two putative interaction interfaces on opposite sides of the kalata B2 molecule, one involving a hydrophobic interaction with the Phe6, and the second involving a charge-charge interaction with the Asp25 residue. An understanding of the factors affecting solution aggregation is of vital importance for future pharmaceutical application of these molecules.

Direct measurement of polymer segment orientation and distortion in shear: semi-dilute solution behavior

The shear induced backbone segment orientation and deformation of the polymeric chromophore diacetylene 4-butoxycarbonylmethylurethane (4BCMU) in semi-dilute solution has been measured with an extended dichroism technique. At low shear rates the random coil, visco-elastic polymer shows orientation in the flow direction. At higher shear rates a reduction in the average conjugation length is observed with an increase in the number of segments orienting perpendicular to the flow direction. Novel behavior, which is not consistent with standard models, is observed for this visco-elastic polymer at high shear rates. The results presented are discussed in view of prior experimental and theoretical work.

Synthesis and Characterization of Hyperbranched Poly(ε-caprolactone)s Having Different Lengths of Homologous Backbone Segments

Hyperbranched poly(ε-caprolactone)s (HPCLs) were synthesized by moisture-sensitive catalyst-free polycondensation of AB2 macromonomers, 2,2-bis[ω-hydroxy oligo(ε-caprolactone)methyl]propionic acids. The HPCLs were designed to incorporate different lengths of linear oligomeric segments consisting of 5, 10, and 20 ε-caprolactone monomer units on the branched backbone chains, accordingly named as HPCL-5, -10, and -20, respectively. End-group analyses were performed on 1H NMR spectra of the three HPCLs, which provided information about the average number of ε-caprolactone units incorporated in the AB2 macromonomers and thus the average number of AB2 macromonomer units incorporated in the resulting hyperbranched polymers. Consequently, the absolute values of molecular weights for the HPCLs were calculated. Size exclusion chromatography equipped with multiangle laser light scattering detector (SEC-MALLS) was employed to measure absolute molecular weights and molecular weight distributions of HPCLs. Then, the results were compared with those obtained from 1H NMR end-group analyses, indicating that there was a good agreement between them. From small-angle X-ray scattering (SAXS), the radii of gyration of the HPCLs and their linear counterpart, poly(ε-caprolactone) (LPCL), were determined from the initial slope of the reciprocal of scattered intensity, 1/I(q), vs the square of scattering vector, q2, curves, fit by the Zimm scattering function. The ratio of mean-square radius of gyration of each HPCL to that of LPCL, termed the branching ratio, resulted in the relative degree of branching for individual HPCLs. As the length of linear oligo(ε-caprolactone) segments decreased, the more highly branched polymers were obtained, i.e., in the order of HPCL-5, -10, and -20 from higher to lower degree of branching. The melting temperatures of HPCLs were lower than that of LPCL and decreased with increase in the degree of branching. In contrast, the thermal decomposition temperatures of HPCLs were shown to be higher than that of LPCL, becoming higher as the degree of branching increased.

Identification of a Residue Critical for Maintaining the Functional Conformation of BPTI

The effects of amino acid replacements on the backbone dynamics of bovine pancreatic trypsin inhibitor (BPTI) were examined using 15N NMR relaxation experiments. Previous studies have shown that backbone amide groups within the trypsin-binding region of the wild-type protein undergo conformational exchange processes on the μs time scale, and that replacement of Tyr35 with Gly greatly increases the number of backbone atoms involved in such motions. In order to determine whether these mutational effects are specific to the replacement of this residue with Gly, six additional replacements were examined in the present study. In two of these, Tyr35 was replaced with either Ala or Leu, and the other four were single replacements of Tyr23, Phe33, Asn43 or Asn44, all of which are highly buried in the native structure and conserved in homologous proteins. The Y35A and Y35L mutants displayed dynamic properties very similar to those of the Y35G mutant, with the backbone segments including residues 10–19 and 32–44 undergoing motions revealed by enhanced 15N transverse relaxation rates. On the other hand, the Y23L, N43G and N44A substitutions caused almost no detectable changes in backbone dynamics, on either the ns–ps or ms–μs time scales, even though each of these replacements significantly destabilizes the native conformation. Replacement of Phe33 with Leu caused intermediate effects, with several residues that have previously been implicated in motions in the wild-type protein displaying enhanced transverse relaxation rates. These results demonstrate that destabilizing amino acid replacements can be accommodated in a native protein with dramatically different effects on conformational dynamics and that Tyr35 plays a particularly important role in defining the conformation of the trypsin-binding site of BPTI.

Computation of DNA Backbone Conformations

We present an algorithm for the computation of 2′-deoxyribose-phosphodiester backbone conformations that are stereochemically compatible with a given arrangement of nucleic acid bases in a DNA structure. The algorithm involves the sequential computation of 2′- deoxyribose and phosphodiester conformers (collectively referred to as a backbone ‘segment’), beginning at the 5′-end of a DNA strand. Computation of the possible segment conformations is achieved by the initial creation of a fragment library, with each fragment representing a set of bond lengths, bond angles and torsion angles. Following exhaustive searching of sugar conformations, each segment conformation is reduced to a single vector, defined by a specific distance, angle and torsion angle, that allows calculation of the O1′ position. A given ‘allowed’ conformation of a backbone segment is determined based on its compatibility with the base positions and with the position of the preceding backbone segment. Initial computation of allowable segment conformations of a strand is followed by the determination of continuous backbone solutions for the strand, beginning at the 3′-end. The algorithm is also able to detect repeating segment conformations that arise in structures containing geometrically repeating dinucleotide steps. To illustrate the utility and properties of the algorithm, we have applied it to a series of experimental DNA structures. Regardless of the conformational complexity of these structures, we are able to compute backbone conformations for each structure. Hence, the algorithm, which is currently implemented within a new computer program NASDAC (Nucleic Acids: Structure, Dynamics and Conformation), should have generally applicability to the computation of DNA structures.

Twists, Knots, and Rings in Proteins: STRUCTURAL DEFINITION OF THE CYCLOTIDE FRAMEWORK

In recent years an increasing number of miniproteins containing an amide-cyclized backbone have been discovered. The cyclotide family is the largest group of such proteins and is characterized by a circular protein backbone and six conserved cysteine residues linked by disulfide bonds in a tight core of the molecule. These form a cystine knot in which an embedded ring formed by two of the disulfide bonds and the connecting backbone segment is threaded by a third disulfide bond. In the current study we have undertaken high resolution structural analysis of two prototypic cyclotides, kalata B1 and cycloviolacin O1, to define the role of the conserved residues in the sequence. We provide the first comprehensive analysis of the topological features in this unique family of proteins, namely rings (a circular backbone), twists (a cis-peptide bond in the Möbius cyclotides) and knots (a knotted arrangement of the disulfide bonds).

Optimal Chain Architectures for the Molecular Design of Functional Polymer Surfaces

The Scheutjens−Fleer self-consistent mean-field theory is used to calculate the surface segregation of various chemical functional moieties located on functional polymers of different architectures. Our results demonstrate the importance of the number and location of functional groups and their surface preference relative to polymer backbone segments in determining surface segregation. In general, we conclude that adjacency of similar functional groups is the most effective means for enhancing surface segregation of functional groups and that having two functional groups of similar character is always preferable to having two functional groups of opposite character, the Pushmi-Pullyu architecture, where one group prefers the surface while the other is repelled from it. The calculations demonstrate that the optimal architecture for producing a low-energy release surface is a functional polymer with adjacent low-energy functional groups located at one chain end. In this situation, both enthalpic and entropi...

Catalytic Oxidative Polymerization of 1,1-Diphenylethylene at Ambient Temperature and Potential Application of Peroxide Macroinitiator

The Co(II)TPP(Py) complex was used as an efficient dioxygen carrier for the radical polymerization of 1,1-diphenylethylene (DPE), which has a low ceiling temperature, at ambient temperature and low oxygen pressure. The mechanism of polymerization is discussed on the basis of kinetic data, UV−vis, ESR, and 1H NMR studies. The rate of polymerization (Rp) and number-average molecular weights (Mn) of poly(1,1-diphenylethylene peroxide) (PDPEP) are higher and the polydispersity is lower than in 2,2‘-azobis(isobutyronitrile) (AIBN) initiated polymerization. PDPEP was further used as a macroinitiator for the polymerization of MMA. The polymerization obeys classical kinetics. The K2 value of the PDPEP has been determined from the slope of Rp2 vs [M]2[I], which reveals that it can also be used at higher temperature for the polymerization. An “active” PMMA was also synthesized, containing initiating segments in the polymer backbone.

Structural Preorganization of Peptide Nucleic Acids: Chiral Cationic Analogues with Five- or Six-Membered Ring Structures

The advent of aminoethylglycyl peptide nucleic acids, aegPNAs, as strong and specific DNA/RNA binding agents has triggered much research activity directed towards the development of PNA-based antisense/antigene therapeutics. These efforts have mainly been directed towards further refinement of aegPNA properties such as water solubility, cellular uptake and discrimination between parallel and antiparallel binding modes. Introduction of chirality and also of positive/negative charges in the PNA backbone has met with some success in this direction. The conformational freedom in the nucleobase linker arm and in the backbone aminoethyl and glycyl segments in the aegPNA backbone were found to be causes of unfavourable entropic loss during complex formation. Suitable clamping in the aegPNA backbone may reduce entropic loss and help produce a conformation appropriate for maximum enthalpic benefits from nucleobase recognition. Introduction of constraint by means of five- or six-membered ring structures in the aegPNA and their contributions to maintaining the balance between rigidity and flexibility in the backbone have shown interesting effects on the overall stability of PNA-DNA/RNA complexes. This review presents an account of the literature in this direction. The significant promise of our approach, which makes use of the naturally occurring trans-4-hydroxy-L-proline to arrive at different chirally pure cyclic PNA analogues, is presented in this review, together with the DNA binding properties of the compounds. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)