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Background New onset atrial fibrillation (NOAF) is not a so rare condition among patients hospitalized for ST-segment elevation myocardial infarction (STEMI). Several studies showed that NOAF during an acute coronary syndrome (ACS) leads to increased mortality, both at short and long term. The indications for the treatment of patients with known AF undergoing percutaneous coronary interventions (PCI) are clear, while less is available about the management of NOAF during ACS and in particular during STEMI. The purpose of this study is therefore to evaluate mortality and clinical outcome of this high risk subgroup of patients. Methods We analysed 1455 consecutive patients undergoing coronary angiography and/or PCI for STEMI. CHA2DS2-VASc and HAS-BLED scores were calculated for all patients. In-hospital, 1-year and long-term follow up mortality was evaluated for all patients. Cerebral ischemic and hemorrhagic events were also evaluated as clinical endpoints at 1 year. Results NOAF was detected in 102 subjects, 62.7% males, with a mean age of 74.8±10.6 years. We found a high prevalence of main cardiovascular risk factors such as hypertension, dyslipidemia, smoke and renal failure. Mean ejection fraction (EF) was 43.5±12.1% and the mean atrial volume was increased (58±20.9 ml). The most represented type of MI at admission was anterior STEMI (46%). NOAF occurred mainly in the peri-acute phase and had a very variable duration (8.1±12.5 min). During hospitalization all patients were treated with Enoxaparin, but only 25.2% of them were discharged with long term oral anticoagulation (16.7% warfarin, 4.9% direct oral anticoagulant). The majority of patients had a CHA2DS2-VASc score >2 and a HAS-BLED score of 2 or 3. In-hospital mortality was 14.2%, while 1-year mortality was 17.2% and long term mortality 32.1% (median follow-up time 1820 days, range 341 to 3985). Through a logistic regression analysis we identified age as an independent predictor of mortality both at short and long term follow up, while EF was the only independent predictor for in-hospital mortality and arrhythmia duration for 1-year mortality. At 1-year follow up we recorded three ischemic strokes, while no bleeding complications. Conclusions STEMI patients who develop NOAF are a very high-risk population and are characterized by increased short and long term mortality. NOAF should be diagnosed and treated as soon as possible with a correct indication to long term OAC based on the ratio between ischemic and hemorrhagic risk. Funding Acknowledgement Type of funding sources: None.

D-amino acids have been detected in a variety of peptides synthesized by animal cells. These include opiate and antimicrobial peptides from amphibian skin, neuropeptides from snail ganglia, an hormone from crustaceous, and a constituent of spider venom. DNA cloning has shown that at those positions where a D-amino acid is found in the end product, a normal codon for the corresponding L-amino acid is present. This implies that the D-residue are formed from L-amino acid by a post-translational reaction. A prototype enzyme has been isolated from the venom of the funnel web spider. An unusual modification in Conus peptides is the post-translational conversion of an L to a D amino acid which has been found in the I-conotoxin superfamily [1]. A potential correlation between the identity of the gene superfamily to which the I-conotoxin belongs and the presence or absence of a D-amino acid in the primary sequence is observed. The great diversity of the I-conopeptide sequence provides a rare opportunity for defining parameters that may be important for this most stealthy of all post-translational modifications. The results indicate that neither the chemical nature of the side chain nor the precise vicinal sequence around the modified residue seem to be critical, but there may be favoured loci for isomerization to a D-amino acid. Here we report about homologues sequences of the native peptide conotoxin, which is agonist toward neurotensin receptors, having L-leucine on the third amino acid from the C-terminus and the isomer with D-leucine in the same position. The conformational analysis of both sequences provide important insight in order to identify the structures and conformational changes involved in the binding with neurotensin receptors.

The recent findings of chiral self-assembling peptides' remarkable chemical complementarity and structural compatibility make it one of the most inspired designer materials and structures in nanobiotechnology. The emerging field of designer chemistry and biology further explores biological and medical applications of these simple D,L-amino acids through producing well defined nanostructures under physiological conditions. Designer materials that are self-assembled molecules by molecule (or atom by atom) to produce novel supramolecular architectures belong to the "bottom-up" instead of the "top-down" approach and likely become an integral part of materials manufacture. This approach requires a deep understanding of individual molecular building blocks, their structures and dynamically assembly properties. The ability to control precisely the functionalization of the monomer building block is critical for control over all other levels of assembly. Chemical functionality and patterning coded in a peptide's amino acid sequence lead to control over conformation. Chemistry and conformation together control self-assembly and nanostructure. All of these together determine a material's bulk mechanical properties. Therefore, careful design of a peptide sequence should, through this bottom-up approach, allow one to control the macroscopic properties of a material. The approach presented here uses multidomain peptides that are designed to have forces favouring the assembly (hydrophobic packing, hydrogen bonding and steric effect), balanced by forces working against assembly (electrostatic repulsion). With proper balancing of these forces it is possible to control the assembly of the peptides into nanofibers. Here we highlight the design principals at the molecular level, the molecular and fine material structures, interactions of the peptides, the dynamic self-assembly behaviours, but also how we can further improve their designs.

When planning an open excavation in granular soils below ground water level, one of the main design concerns refers to water seepage from the bottom. Such a seepage may cause local piping, subsidence of the surrounding area with undesired settlements of nearby buildings, or a water inflow which may interfere with constructional operations. The adoption of continuous jet grouted bottom plugs is by far the most effective way to solve this critical design issue, and its use is constantly increasing in underground works. In this paper, the example of Tribunale station is reported and discussed. It is shown that rational design can be best carried out using a deterministic approach to cope with code indications on equi-librium (i.e. uplift and structural cracking), while the choice of the spacing among columns cannot be but probabilistic. By using Jetplug, a numerical code developed at the University of Naples Federico II to simulate probabilistically the behavior of a plug made of any number of columns, it was possible to estimate the water inflow through the plug as a function of the spacing among columns. By assigning the maximum tolerable inflow, the spacing could be selected on a cost effectiveness basis, assuming a risk compatible with Eurocode’s indications.

Elastomeric proteins are characterized by their large extensibility before rupture, reversible deformation without loss of energy, and high resilience upon stretching. Motivated by their unique mechanical properties, there has been tremendous research in understanding and manipulating elastomeric polypeptides, with most work conducted on the elastin but more recent work on an expanded set of polypeptide elastomers and it has been possible to manipulate the physical properties and conformation of these material. The literature data and analyses [1] affirm that components of elastin, and purified elastin fiber itself contain dynamic, non-random, regularly repeating structures that exhibit dominantly entropic elasticity by means of a damping of internal chain dynamics on extension. The resulting structure, termed ?-spiral, as the ?-turn is the dominant repeating secondary structural feature. These studies revealed the presence of two different types of conformers; folded or semi-folded conformation consisting of ?-turns and extended conformations. Interestingly, Tatham and coworkers[1] have shown that the elastic modulus of HMW wheat gluten subunits crosslinked by ?-irradiation, similar to that of the crosslinked elastin polypentapeptide poly(VPGVG). Wheat glutenin is the main elastomeric protein in plants. The high molecular weight (HMW) subunits of wheat gluten are seed storage proteins, for storage of essential nutrients such as carbon, nitrogen and sulfur for growth of seedlings. The hexa-amino-acid repeats PGQGQQ and the nona-amino-acid repeats GYYPTSPQQ in the protein are considered to be mainly responsible for the elasticity of wheat gluten[2]. CD and FTIR spectroscopy on the short peptides based on the repeat motifs of the HMW subunits of gluten suggested the presence of ?-turns between the repeats. The glutenin contains repetitive ?-turns which could lead to formation of ?-spirals as hypothesized for elastin [2], but in addition to the entropic component, enthalpic contributions related to the extensive hydrogen bonding within and between the subunits is also proposed to contribute to the total elastomeric force .

De novo design of existing or novel peptide folds demand a thorough understanding of the rules that underlie protein structure and stability. The recurring theme in many design strategies is the use of amino acid propensities to adopt various secondary structures. There are many occasions in the literature where affinity is enhanced through hydrophobic interactions, even at the expense of hydrogen bonds. Literature data support the hypothesis that the balance of contribution between polar and hydrophobic interactions is determinant in molecular recognition. During the last twenty years a variety of "nonclassical" exogenous opioid peptides derived from enzymatic digest of various food protein sources has been demonstrated.[1] Most of the food-derived opioids are peptides fragments of milk proteins (caseins, ?-lactalbumin, ?-lactoglobulin, lactotransferrin).[2]. In our ongoing work with bioactive peptides derived from milk proteins[3] we have observed the structural, conformational, and dynamic properties of ?-lactorphin and ?-lactorphin, that derived from whey protein ?-lactalbumin and ?-lactoglobulin respectively. As found for ?-lactorphin also ?-lactorphin showed affinity for opioid receptors and was found to behave like a µ-opioid receptor agonist. We present here results of a NMR study of Boc- and -OMe protect analogues of ?-lactorphin and ?-lactorphin which provide useful informations about conformational behaviour in solution. Our interpretation has been aided by similar study of analogues containing conformational constrictions due to the presence of prolyl residue(s) and of dimeric octapeptide of ?-lactorphin. References 1.H.S. Gill, F.Doull, K.J. Rutherfurd, M.L.Cross British J. of Nutrition(2000) 84 (Suppl.1), S111-S117 2.H.Meisel Biopolymers (1997) 240, 119-128 E.Fenude, S.Dedola, M.Fais Congress "Complex Systems: structure,properties, reactivity, and dynamics"(2005) Alghero, 13-15/06/2005 3. G. Micera, D. Sanna, & al, Journal of Inorganic Biochemistry(1998) 69, 91-95

The majority of immune systems mediators are polypeptide or proteins by nature. They serve as messengers in the signal transfer between various immunocompetent cells providing cell cooperation during the development of the immune responses. Peptide and polypeptide molecules are implicated in an intricate network of bioregulatory processes resulting in homeostasis. The biological function ("function" code) of biologically active peptides is determined by the conformations coded in their primary structure ("structure" code). Biologically active fragments originating from food proteins should be taken into account as potential modulators of various regulatory processes in the body. In contrast to endogenous bioactive peptides, many food-derived sequences reveal multifunctional properties -i.e. specific peptide sequences having two different biological activity have been reported. In the following table are reported few sequences used in this work. ProteinFragmentNameBiological ActivityRef. beta-Casein(60-66) YPFPGPIbeta-Casomorphin-7Opioid, Immunomodulatory1,2,5 beta-Casein(191-193) LLYImmunopeptideImmunomodulatory1 beta-Lactoglobulin(102-105) YLLFbeta-LactorphinOpioid Agonist1,3 beta-Haemoglobin(31-35) LVVYPLVV-HemorphinOpioid, Immunomodulatory4 It is well accepted that the binding of the ligand to its receptor is mediated by hydrogen bonding, hydrophobic interactions, and shape complementarity, but the relative contribution of each of these interactions is still poor understood for the bioactive sequences here observed. In our work on synthetic opioid peptides we studied conformational behavior of following conventionally protected sequences: -LVVYP-, -LVVY-, -LVVF-,-LLY-, and -LLF-. These products have been synthesized, purified, and then analyzed by NMR spectroscopy, employing both mono- and bi-dimensional techniques. The results obtained are here compared and discussed. References 1.H.Meisel Biopolymers (1997) 43, 119-128 2.E.Fenude, Roggio A.M., XII° National Congress of Società Chimica Italiana (2006), Firenze 10-15/09/2006 3.E.Fenude, S.Dedola, M.Fais Congress "Complex Systems: structure,properties, reactivity, and dynamics"(2005) Alghero, 13-15/06/2005 4.R.V.Petrov, A.A.Mikhailova, L.A. Fonona, Biopolymers (1997) 43, 139-146. 5. G. Micera, D. Sanna, & al, Journal of Inorganic Biochemistry(1998) 69, 91-95

Turquoise is a hydrated copper aluminum phosphate and belongs to a group of minerals, the turquoise group, consisting of at least six isostructural end-members. Turquoise is common in the American Southwest, Iran and Egypt, where most of its value is associated with art, jewelry and ancient culture. When affected by near-surface conditions and extended exposure to sunlight and meteoric (rain) water, turquoise weathers to chalky white clay minerals. This alteration affects identification of the provenance regions of archaeologically recovered turquoise artifacts, the mineralogical properties of turquoise, and the value of turquoise as a semi-precious gemstone. However, this alteration process is poorly understood. Therefore, to improve the characterization of turquoise provenance for archaeological and gemological purposes, it is important to understand the alteration processes that affect turquoise. The general formula for the turquoise group can be written as A0–1B6(PO4)4(OH)8∙4H2O with Cu2+ or Fe2+ as the most common constituents at the A position and Al3+ and Fe3+ at the B position. However, Ca2+ or Zn2+ can occur at the A position in some of the more rare members of the turquoise group. The range in chemical composition (different concentrations of Cu, Fe, and Al) of turquoise (latu sensu) produces a wide range of colors. Foord and Taggart (1998) suggest that differ¬ences in the Cu and Fe ratio are responsible for the differences in color of the samples: blue turquoise has Cu at the A position and Al at the B position, whereas green turquoise (chalcosiderite) largely contains Fe3+ at the B position. The crystal structure of turquoise is triclinic, space group P¯1. Different site nomenclatures have been used in many of the structural and spectroscopic studies of the minerals of the turquoise group, depending on the chemical compositions under study. The turquoise samples belong to the collection of the Real Museo Mineralogico (RMM), Centro Musei delle Scienze Naturali, Università degli Studi di Napoli Federico II. Five turquoise samples covering a wide range of compositions in the turquoise group and in provenance were analyzed by X ray diffraction (XRD), electron microprobe analysis (EMPA), BSE-SEM-EDS analysis, LA-ICP-MS analysis and Fourier transform infrared (FTIR) spectroscopy. The provenances of the turquoise samples used in this study are: Tur 1 (RMM catalogue E5683) Sinai, Egitto; Tur 2 (E7666) Santa Fè S. Miguel, New Mexico; Tur 3 (E1675) Sassonia, Germania; Tur 4 (E7272) Montebras Creuse, Francia; Tur 5 (E1670/13131) Nischapir, Khorassan, Iran. The colors of Tur 1 sample are blue-green and light blue. The EMPA analysis show the presences in Tur 1 of faustite, altered turquoise, crandallite, quartz and magnetite. The turquoise samples display evidence of alteration from weathering processes, showing deficiencies in both cations and anion groups, indicated by EMPA, but preserving the crystal structure of turquoise, as verified by XRD. They also show large amounts of Si and Ca in their microprobe data, due to the presence of quartz and Ca crandallite, respectively, which are identified by XRD analyses. The chemical analysis show the presences in Tur 2, that is blue-green and white, of: turquoise, turquoise ferrian, ferrian variscite, variscite. The XRD analyses indicate the presence also of metavariscite and planerite. Locally in the fracture the EDS-BSE analyses show the presence of iron sulfates and potassium rich silcates. For Tur 3 sample, apple green and light green coloured, the EMPA analysis indicate the presences of Chalcosiderite and variscite; the XRD analyses show the presence also of metavariscite. The colors of Tur 4 sample is turquoise blue, pale blue and white. The EMPA analysis show the presences of turquoise, variscite and wavellite, the XDR pattern also of metavariscite, planerite and quartz. Blue-green, turquoise blue and pale blue Tur 5, on the basis of EMPA analysis is composed by turquoise and ferrian turquoise, the XRD also by metavariscite, planerite and quartz. The EDS-BSE analyses confirm the presence of quartz and cuprian planerite in the fracture of the sample. The pattern of REE elements indicate similarities between Tur 4 and Tur 1, and between Tur 2 and Tur 5. The trace elements particularly V, Ti, Mn, Cr, Ga for the turquoise minerals group, would be useful to be able to distinguish the samples from different localities. Powder samples for FTIR study were prepared as KBr pellets. The spectra are different on the bases of the mineralogical composition of the turquoise samples analyzed. From what has been published spectra closer to the typical turquoise are those Tur 1, Tur 2 and Tur 5. The Tur 4 begins to differentiate more clearly, and finally the Tur 3 is clearly different and seems to be similar to that of variscite. Particularly the absorption frequencies of OH and H2O show marked variations in both the width of the bands in the presence of different components. High-frequency components appear at least 4 (3509, 3494, 3467 and 3448 cm-1) due to the OH groups. They are well resolved in Tur 1 but less so in Tur 5 and Tur 2. In Tur 4 and then definitively in Tur 3 these components are absent altogether, while appears a new component shifted to higher frequency (3584 cm-1). Still in Tur 1, Tur 5 and Tur 2 are two bands rather wide low frequency (3300 and 3104 cm-1) due to the absorption of the molecules of H2O. In Tur 4 Tur 3 and these components are not obvious, but seem to be replaced by components centered at different frequencies, due to the presence of H2O. For the absorption frequencies in the region of the polyhedra Tur 1, Tur 5, Tur 2, Tur 4 and Tur 3 is observed a gradual decrease of the components that constitute the strong absorption centered around 1100 cm-1 (due to the vibrations of the groups PO43-). Substantial differences can still be seen in the region between 800 and 400 cm-1 between samples Tur 1, Tur 5, Tur 2 and samples Tur 4 and Tur 3.

A suite of twelve vesuviante samples from skarn and syenitc ejecta from the Somma- Vesuvius volcanic complex was studied by means of a combination of energy dispersive spectrometry (EDS), inductively-coupled plasma-mass spectrometry (ICP-MS), powder and single-crystal X-ray diffraction, polarized radiation Fourier-transform infrared (FTIR) singlecrystal micro-spectrometry. Some thermo-gravimetric analyses (TGA) were also performed. Vesuvianite crystals are dark brown to honey yellow-brown, rarely reddish-brown, and up to 2 centimetres in dimension. Their major elements (SiO 2, Al 2O 3, CaO and MgO) composition is rather constant, while Fe 2O 3, MnO and TiO 2 are slightly more variable. Light elements (B, Be and Li), Y, REE and actinides (Th, U) have been detected in all samples in minor to trace amounts, together with V, Zn, Zr, Sn, Co, Ga, Nb, Ta, Hf, Pb and Bi. Among the volatiles, fluorine is prevailing (in a range 1.41-2.25 wt. %). Water and chlorine are always observed, in the range 0.67-1.03 wt. % and 0.01-0.05 wt. %, respectively. Single-crystal X-ray diffraction analyses of vesuvianite gave P4/nnc as the most probable space group. Cell parameters vary from 15.542 Å up to 15.576 Å for a and 11.800 Å up to 11.827 Å for c. Polarized FTIR spectra of the OH fundamental measured parallel to the c-axis are dominated by absorption bands at 3638, 3567, 3452 and 3200 cm -1, with two additional bands centred at 3590 and 3117 cm -1. All bands show strong pleochroism with maximum absorption parallel to the c-axis and weak absorption components perpendicular to c. The spectra measured perpendicular to the c-axis are also dominated by the 3567, 3590 and 3638 cm -1 band group. OH amounts have been calculated using the total integrated absorption coefficient derived from the fitted spectra.These contents are in good agreement with the H 2O values obtained by TGA. The formation temperature and the chemical environment of vesuvianite point to at least 800-890 °C and to the occurrence of chloride-fluoride-sulfate-carbonate-rich saline fluids, which are also rich in incompatible elements.

Radioimmunotherapy, also known as systemic targeted radiation therapy, uses antibodies, antibody fragments, or compounds as carriers to guide radiation to the targets. It is a topic rapidly increasing in importance and success in treatment of cancer patients. This book represents a comprehensive amalgamation of the radiation physics, chemistry, radiobiology, tumor models, and clinical data for targeted radionuclide therapy. It outlines the current challenges and provides a glimpse at future directions. With significant advances in cell biology and molecular engineering, many targeting constructs are now available that will safely deliver these highly cytotoxic radionuclides in a targeted fashion

Communities of practices (CoPs) bring high value to product and process innovation in the actual context of economic depression and enable the development of small and medium enterprises. We aim to contribute to the improvement of their value promoting an integrated model based on vSa and DKMF models finalized to promote the knowledge transfer among community members of cooperating CoPs. The model enables to generate new knowledge and to amplify innovative cooperation when the governance effort in planning community development finds an equilibrium with structural characteristic of meta-CoP emerging from cooperating CoPs. The model is expected to help with needs of next organization scenario: big projects collecting activities shared between many actors and emerging complex social systems based on networking.

he design of new peptides (QK) targeting two protein systems deeply involved in angiogenesis: integrins and vascular endothelial growth factor receptors is presented. Integrins are cell surface receptors that mediate adhesion of endothelial cells to the extracellular matrix and to the adjacent cells through the interaction with Arg-Gly-Asp (RGD) sequence found within many extracellular matrix protein (i.e. vitronectin). It was shown that integrin avb3 together with avb5 are overexpressed on tumor cells and endothelial cells of the tumor neovasculature, acting as angiogenic markers. It is of great therapeutic and diagnostic interest to develop new compds. able to discriminate between avb3 and avb5. NMR anal. revealed that QK adopts a helical conformation in water, whereas the peptide corresponding to the helix region of VEGF (VEGF15) is unstructured. The conformation of the designed peptide exactly corresponds to the N-terminal helix of VEGF when complexed with Flt-1. Binding studies showed that QK competes with VEGF for a binding site on EC membranes and activates both receptors similarly to VEGF. VEGF15 do not bind to the receptors indicating that the helical structure is necessary for the biol. activity. Cells proliferation expts. and the downstream activation of VEGF-dependent intracellular pathway (ERK1/2) confirmed the agonist behavior of the peptide. Results indicate that QK peptide is able to recapitulate many of the features in signal transduction that are reported for VEGF. The new peptide-based mols. reported may represent the lead compds. for the development of novel angiogenesis modulating drugs for application in diagnostic and targeted therapy.

Two complete series of N-protected oligopeptide esters to the pentamer level from 1-amino-cyclodecane-1-carboxylic acid (AC10C), an α-amino acid conformationally constrained through a medium-ring Ciα↔Ciα cyclization, and either the L-Ala or Aib residue, along with the N-protected AC10c monomer and homo-dimer alkylamides, were synthesized using solution methods and fully characterized. The preferred conformation of these model peptides was assessed in deuterochloroform solution using FT-IR absorption and 1H NMR techniques. Furthermore, the molecular structures of two derivatives (Z-AC10c-OH and Fmoc-Ac10c-OH) and two peptides (the dipeptide ester Z-Ac10C-L-Phe-OMe and the tripeptide ester Z-Aib-Ac10c-Aib-OtBu) were determined in the crystal state using X-ray diffraction. The experimental results support the view that β-bends and 310-helices are preferentially adopted by peptides rich in Ac10c, the third largest cycloaliphatic Cα,α-disubstituted glycine known. This investigation allowed us to complete a detailed conformational analysis of the whole 1-amino-cycloalkane-1-carboxylic acid (ACnC, with n=3-12) series, which represents the prerequisite for our recent proposal of the 'ACnC scan' concept.

Recent studies on the conformational preferences of the Dϕg (Cα,α-diphenylglycine) residue showed that this Cα,α-disubstituted glycine has a structural versatility. In fact, depending on the nature of the following or preceding residue, Dϕg can assume either folded or extended conformations. We have carried out the analysis of the conformational preferences of the Dϕg residue in tripeptides containing consecutive Dϕg residues. The crystal structures of Z–Dϕg–Dϕg–Dϕg–OMe (a; Z = benzyloxycarbonyl; OMe = methyl ester), Z–Aib–Dϕg–Dϕg–OMe (b; Aib = α-aminoisobutyric acid), and Z–Ac3c–Dϕg–Dϕg–OMe (c; Ac3c = α-amino-cyclopropan carboxylic acid), are here reported. The Dϕg residues adopt the fully extended conformation in the three tripeptides examined. Together with our previous findings on Dϕg containing peptides, the structures of the peptides here examined, indicate that the presence of adjacent Dϕg residue in the sequence further stabilizes the extended conformation.

The reaction of 39,59-di-O-acetylthymidine with [Pt(PPh3)4] and KCl yielded a platinum(II) complex where the platinum is co-ordinated to the nucleobase through the N3 atom. In a similar reaction 1-methylthymine (1-MeThy) furnished the complex cis-[PtCl(1-MeThy)(PPh3)2], whose structure was determined by spectroscopic data and single crystal X-ray diffraction. When 1-MeThy was treated with [Pt(PPh3)4] in the absence of chloride ions the complex trans-[Pt(OH)(1-MeThy)(PPh3)2] was obtained.

To identify the peptide conformation that is preferentially recognized by the receptor, we have synthetized by solidphase method a series of deltorphin I analogs with increasing selectivity for δ- and μ-opioid receptor. Structure-selectivity relationship of these peptides were evaluated on the basis of receptor-binding properties and conformational features, computed by two-dimensional NMR spectra and distancegeometry techniques. These compounds in solution are present with a large number of conformers with no defined secondary structural elements. The analysis of the average properties of these compounds indicate the presence of some distinct conformational preferences that can be related to the observed opioid receptor selectivities. Selectivity for the δ-and μ-opioid receptors can be ascribed to the spatial arrangement of the aromatic moieties. In addition, substitutions in position 2 and 4 are important for the correct arrangement and must be taken into account in the design of δ-opioid receptor-selective ligands.

The crystal structures of three fully protected tripeptides containing the Dϕg residue (Cα,α-diphenylglycine) in the central position are reported, namely Z-Gly-Dϕg-Gly-OMe (a), Z-Gly-Dϕg-Aib-OMe (b) and Z-Aib-Dϕg-Aib-OMe (c). The molecular conformations are quite unusual because the Dϕg residue adopts a folded conformation in the 310-helical region when the following residue adopts a folded conformation of opposite handedness (peptidesbandc). In contrast, the Dϕg residue adopts the more frequently observed fully extended conformation when the following residue adopts a semi-extended conformation (peptidea). These findings are in agreement with the theoretical calculations on Ac-Dϕg-Aib-NHCH3 and Ac-Aib-Dϕg-NHCH3 also reported in this work.