Synthesis and receptor binding of opioid peptide analogues containing β3‐homo‐amino acids

β‐Amino acids containing hybrid peptides and β‐peptides show great potential as peptidomimetics. In this paper we describe the synthesis and affinity toward the µ‐ and δ‐opioid receptors of β‐peptides, analogues of Leu‐enkephalin, deltorphin I, dermorphin and α,β‐hybrides, analogues of deltorphin I. Substitution of α‐amino acid residues with β³‐homo‐amino acid residues, in general resulted in decrease of affinity to opioid receptors. However, the incorporation β³h‐D ‐Ala in position 2 or β³hPhe in position 3 of deltorphin I resulted in potent and selective ligand for δ‐opioid receptor. The NMR studies of β‐deltorphin I analogue suggest that conformational motions in the central part of the peptide backbone are partially restricted and some conformational preferences can be expected. Copyright © 2009 European Peptide Society and John Wiley & Sons, Ltd.     

The S-methylmethionine cycle in angiosperms: ubiquity, antiquity and activity

Angiosperms synthesize S-methylmethionine (SMM) from methionine (Met) and S-adenosylmethionine (AdoMet) in a unique reaction catalyzed by Met S-methyltransferase (MMT). SMM serves as methyl donor for Met synthesis from homocysteine, catalyzed by homocysteine S-methyltransferase (HMT). MMT and HMT together have been proposed to constitute a futile SMM cycle that stops the free Met pool from being depleted by an overshoot in AdoMet synthesis. Arabidopsis and maize have one MMT gene, and at least three HMT genes that belong to two anciently diverged classes and encode enzymes with distinct properties and expression patterns. SMM, and presumably its cycle, must therefore have originated before dicot and monocot lineages separated. Arabidopsis leaves, roots and developing seeds all express MMT and HMTs, and can metabolize [35S]Met to [35S]SMM and vice versa. The SMM cycle therefore operates throughout the plant. This appears to be a general feature of angiosperms, as digital gene expression profiles show that MMT and HMT are co-expressed in leaves, roots and reproductive tissues of maize and other species. An in silico model of the SMM cycle in mature Arabidopsis leaves was developed from radiotracer kinetic measurements and pool size data. This model indicates that the SMM cycle consumes half the AdoMet produced, and suggests that the cycle serves to stop accumulation of AdoMet, rather than to prevent depletion of free Met. Because plants lack the negative feedback loops that regulate AdoMet pool size in other eukaryotes, the SMM cycle may be the main mechanism whereby plants achieve short-term control of AdoMet level.     

High‐Efficiency Polymer Homo‐Tandem Solar Cells with Carbon Quantum‐Dot‐Doped Tunnel Junction Intermediate Layer

The tunnel junction (TJ) intermediate connection layer (ICL), which is the most critical component for high‐efficient tandem solar cell, generally consists of hole conducting layer and polyethyleneimine (PEI) polyelectrolyte. However, because of the nonconducting feature of pristine PEI, photocurrent is open‐restricted in ICL even with a little thick PEI layer. Here, high‐efficiency homo‐tandem solar cells are demonstrated with enhanced efficiency by introducing carbon quantum dot (CQD)‐doped PEI on TJ–ICL. The CQD‐doped PEI provides substantial dynamic advantages in the operation of both single‐junction solar cells and homo‐tandem solar cells. The inclusion of CQDs in the PEI layer leads to improved electron extraction property in single‐junction solar cells and better series connection in tandem solar cells. The highest efficient solar cell with CQD‐doped PEI layer in between indium tin oxide (ITO) and photoactive layer exhibits a maximum power conversion efficiency (PCE) of 9.49%, which represents a value nearly 10% higher than those of solar cells with pristine PEI layer. In the case of tandem solar cells, the highest performing tandem solar cell fabricated with C‐dot‐doped PEI layer in ICL yields a PCE of 12.13%; this value represents an ≈15% increase in the efficiency compared with tandem solar cells with a pristine PEI layer.     

Understanding the External Quantum Efficiency of Organic Homo‐Tandem Solar Cells Utilizing a Three‐Terminal Device Architecture

A fundamental analysis of the external quantum efficiency (EQE) of organic tandem solar cells with equal absorbers in both subcells (homo‐tandem solar cells) is presented. Providing direct access to both subcells by introducing a conductive intermediate polymer electrode into the recombination zone, without changing the optical and electric device properties, the three‐terminal device becomes a proxy to the two‐terminal tandem solar cell properties. From the spectrally resolved EQE of the subcells in three‐terminal configuration wavelength and intensity of suitable bias light as well as bias voltage are determined that in turn allow for accurate EQE measurements of the common two‐terminal tandem solar cells. Theoretic considerations allow the prediction of the tandem solar cell's EQE from its subcells' EQEs as well as the prediction of the tandem cell EQE under monochromatic bias light illumination being in excellent agreement with experimental results. All findings discussed herein can be applied to more common hetero‐tandem solar cell architectures likewise.     

Systematic solution to homo‐oligomeric structures determined by NMR

Protein structure determination by NMR has predominantly relied on simulated annealing‐based conformational search for a converged fold using primarily distance constraints, including constraints derived from nuclear Overhauser effects, paramagnetic relaxation enhancement, and cysteine crosslinkings. Although there is no guarantee that the converged fold represents the global minimum of the conformational space, it is generally accepted that good convergence is synonymous to the global minimum. Here, we show such a criterion breaks down in the presence of large numbers of ambiguous constraints from NMR experiments on homo‐oligomeric protein complexes. A systematic evaluation of the conformational solutions that satisfy the NMR constraints of a trimeric membrane protein, DAGK, reveals 9 distinct folds, including the reported NMR and crystal structures. This result highlights the fundamental limitation of global fold determination for homo‐oligomeric proteins using ambiguous distance constraints and provides a systematic solution for exhaustive enumeration of all satisfying solutions. Proteins 2015; 83:651–661. © 2015 Wiley Periodicals, Inc.     

Morphometric variation in Plio-Pleistocene hominid distal humeri

The magnitude and meaning of morphological variation among Plio-Pleistocene hominid distal humeri have been recurrent points of disagreement among paleoanthropologists. Some researchers have found noteworthy differences among fossil humeri that they believe merit taxonomic separation, while others question the possiblity of accurately sorting these fossils into different species and/or functional groups. Size and shape differences among fossil distal humeri are evaluated here to determine whether the magnitude and patterns of these differences can be observed within large-bodied, living hominoids. Specimens analyzed in this study have been assigned to various taxa (Australopithecus afarensis, A. africanus, A. anamensis, Paranthropus, and early Homo) and include AL 288-1m, AL 288-1s, AL 137-48a, AL 322-1, Gomboré IB 7594, TM 1517, KNM-ER 739, KNM-ER 1504, KMN-KP 271 (Kanapoi), and Stw 431. Five extant hominoid populations are sampled to provide a standard by which to consider differences found between the fossils, including two modern human groups (Native American and African American), one group of Pan troglodytes, and two subspecies of Gorilla gorilla (G. g. beringei, G. g. gorilla). All possible pairwise d values (average Euclidean distances) are calculated within each of the reference populations using an exact randomization procedure. This is done using both raw linear measurements as well as scale-free shape data created as ratios of each measurement to the geometric mean. Differences between each pair of fossil humeri are evaluated by comparing their d values to the distribution of d values found within each of the reference populations. Principal coordinate analysis and an unweighted pair group method with arithmetic averages (UPGMA) cluster analysis are utilized to further assess similarities and differences among the fossils. Finally, canonical variates analysis and discriminant analysis are employed using all hominoid samples in order to control for correlations among variables and to identify those variables that discriminate among groups; possible affinities of individual fossils with specific extant species are also examined. The largest size differences, those between the small Hadar specimens and the two largest fossils (KNM-ER 739, IB 7594), can be accommodated easily within the ranges of variation of the two Gorilla samples, but are extreme relative to the other reference samples. The d values between most of the fossils based on shape data, with the notable exception of those associated with KNM-ER 739 and KNM-ER 1504, can be sampled safely within all five reference samples. Subsequent analyses further support the inference that KNM-ER 739 and KNM-ER 1504 are different from the other hominid humeri and possess a unique total morphometric pattern. In overall shape, the distal humeri of the other fossils (non-Koobi Fora) are most similar to living chimpanzees. The distal humerus of Paranthropus from Kromdraai (TM 1517e) is most similar to one of the Hadar specimens of A. afarensis (AL 137-48a), whereas the first specimen of A. africanus from Sterkfontein (Stw 431) is not closely linked to any of the other australopithecines. The A. anamensis humerus from Kanapoi exhibits no special affinities to A. afarensis or to modern humans. © 1996 Wiley-Liss, Inc.     

Crystal-state conformation of Calpha,alpha-dialkylated peptides containing chiral beta-homo-residues.

Secondary structure formation and stability are essential features in the knowledge of complex folding topology of biomolecules. To better understand the relationships between preferred conformations and functional properties of beta-homo-amino acids, the synthesis and conformational characterization by X-ray diffraction analysis of peptides containing conformationally constrained Calpha,alpha-dialkylated amino acid residues, such as alpha-aminoisobutyric acid or 1-aminocyclohexane-1-carboxylic acid and a single beta-homoamino acid, differently displaced along the peptide sequence have been carried out. The peptides investigated are: Boc-betaHLeu-(Ac6c)2-OMe, Boc-Ac6c-betaHLeu-(Ac6c)2-OMe and Boc-betaHVal-(Aib)5-OtBu, together with the C-protected beta-homo-residue HCl.H-betaHVal-OMe. The results indicate that the insertion of a betaH-residue at position 1 or 2 of peptides containing strong helix-inducing, bulky Calpha,alpha-disubstituted amino acid residues does not induce any specific conformational preferences. In the crystal state, most of the NH groups of beta-homo residues of tri- and tetrapeptides are not involved in intramolecular hydrogen bonds, thus failing to achieve helical structures similar to those of peptides exclusively constituted of Calpha,alpha-disubstituted amino acid residues. However, by repeating the structural motifs observed in the molecules investigated, a beta-pleated sheet secondary structure, and a new helical structure, named (14/15)-helix, were generated, corresponding to calculated minimum-energy conformations. Our findings, as well as literature data, strongly indicate that conformations of betaH-residues, with the micro torsion angle equal to -60 degrees, are very unlikely.     

RDC-assisted modeling of symmetric protein homo-oligomers

Protein oligomerization serves an important function in biological processes, yet solving structures of protein oligomers has always been a challenge. For solution NMR, the challenge arises both from the increased size of these systems and, in the case of homo-oligomers, from ambiguities in assignment of intra- as opposed to intersubunit NOEs. In this study, we present a residual dipolar coupling (RDC)-assisted method for constructing models of homo-oligomers with purely rotational symmetry. Utilizing the fact that one of the principal axes of the tensor describing the alignment needed for RDC measurement is always parallel to the oligomer symmetry axis, it is possible to greatly restrict possible models for the oligomer. Here, it is shown that, if the monomer structure is known, all allowed dimer models can be constructed using a grid search algorithm and evaluated based on RDC simulations and the quality of the interface between the subunits. Using the Bacillus subtilis protein YkuJ as an example, it is shown that the evaluation criteria based on just two sets of NH RDCs are very selective and can unambiguously produce a model in good agreement with an existing X-ray structure of YkuJ.