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High affinity peptide ligands for the bradykinin (BK) B2 subtype receptor have been shown to adopt a β-turn conformation of the C-terminal tetrapeptide (H-Arg1-Pro2-Pro3-Gly4-Phe5-Ser6-Pro7-Phe8-Arg9-OH). We investigated the replacement of the Pro7-Phe8 dipeptide moiety in BK or the D-Tic7-Oic8 subunit in HOE140 (H-D-Arg0-Arg1-Pro2-Hyp3-Gly4-Thi5-Ser6- D-Tic7-Oic8-Arg9-OH) by 4-amino-1,2,4,5-tetrahydro-2-benzazepin-3-one templates (Aba). Binding studies to the human B2 receptor showed a correlation between the affinities of the BK analogs and the propensity of the templates to adopt a β-turn conformation. The L-spiro-Aba-Gly containing HOE140 analog BK10 has the best affinity, which correlates with the known turn-inducing property of this template. All the compounds did not modify basal inositolphosphate (IP) output in B2-expressing CHO cells up to 10 µ M concentration. The antagonist properties were confirmed by the guinea pig ileum smooth muscle contractility assay. The new amino-benzazepinone (Aba) substituted BK analogs were found to be surmountable antagonists. Copyright © 2007 European Peptide Society and John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Chronic pain is one of the most critical health issues worldwide. Despite considerable efforts to find therapeutic alternatives, opioid drugs remain the gold standard for pain management. The administration of μ‐opioid receptor (MOR) agonists is associated with detrimental and limiting adverse effects. Overall, these adverse effects strongly overshadow the effectiveness of opioid therapy. In this context, the development of neurotensin (NT) ligands has shown to be a promising approach for the management of chronic and acute pain. NT exerts its opioid‐independent analgesic effects through the binding of two G protein‐coupled receptors (GPCRs), NTS1 and NTS2. In the last decades, modified NT analogues have been proven to provide potent analgesia in vivo. However, selective NTS1 and nonselective NTS1/NTS2 ligands cause antinociception associated with hypothermia and hypotension, whereas selective NTS2 ligands induce analgesia without altering the body temperature and blood pressure. In light of this, various structure–activity relationship (SAR) studies provided findings addressing the binding affinity of ligands towards NTS2. Herein, we comprehensively review peptide‐based NTS2‐selective ligands as a robust alternative for future pain management. Particular emphasis is placed on SAR studies governing the desired selectivity and associated in vivo results. [ABSTRACT FROM AUTHOR]

The synthesis of new dermorphin analogues is described. The ( R)-alanine or phenylalanine residues of natural dermorphin were substituted by the corresponding α-methyl-β-azidoalanine or α-benzyl-β-azido(1-piperidinyl)alanine residues. The potency and selectivity of the new analogues were evaluated by a competitive receptor binding assay in rat brain using [3H]DAMGO (a μ ligand) and [3H]DELT (a δ ligand). The most active analogue in this series, Tyr-( R)-Ala-( R)-α-benzyl-β-azidoAla-Gly-Tyr-Pro-Ser-NH2 and its epimer were analysed by 1H and 13C NMR spectroscopy and restrained molecular dynamics simulations. The dominant conformation of the investigated peptides depended on the absolute configuration around Cα in the α-benzyl-β-azidoAla residue in position 3. The ( R) configuration led to the formation of a type I β-turn, whilst switching to the ( S) configuration gave rise to an inverse β-turn of type I′, followed by the formation of a very short β-sheet. The selectivity of Tyr-( R)-Ala-( R) and ( S)-α-benzyl-β-azidoAla-Gly-Tyr-Pro-Ser-NH2 was shown to be very similar; nevertheless, the two analogues exhibited different conformational preferences. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The Pictet-Spengler (PS) cyclizations of β³-hTrp derivatives as arylethylamine substrates were performed with L-a-amino and D-a-amino aldehydes as carbonyl components. During the PS reaction, a new stereogenic center was created, and the mixture of cis/trans 1,3-disubstituted 1,2,3,4-tetrahydro-β-carbolines was obtained. The ratio of cis/trans diastereomers depends on the stereogenic centre of used amino aldehyde and the size of substituents. It was confirmed by 1H and 2D NMR (ROESY) spectra. The conformations of cyclic products were studied by 2D NMR ROESY spectra. Products of the PS condensation after removal of protecting group(s) can be incorporated into a peptide chain as tryptophan mimetics with the possibility of the β-turn induction. [ABSTRACT FROM AUTHOR]

We have synthesized a 17-mer peptide (ERα17p) that is issued from the hinge region of the estrogen receptor α and which activates the proliferation of breast carcinoma cells in steroid-deprived conditions. In the present paper, we show that at a concentration of ~50 μM, it rapidly forms amyloid-like fibrils with the assistance of electrostatic interactions and that at higher concentrations, it spontaneously forms a hydrogel. By using biophysical, spectral and rheological techniques, we have explored the structural, biophysical and mechanical characteristics of ERα17p with respect to fibril formation and gelation. Copyright © 2014 European Peptide Society and John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The Pictet-Spengler (PS) reaction was performed with various types of substrates: H-Trp-OMe and dipeptides with N-terminal Trp as arylethylamine components and Z-protected amino aldehydes and peptidoaldehydes as carbonyl components. We found that the C-terminal part of Trp derivatives did not have any influence on the stereoselectivity of the reaction and the results are the same for simple esters of Trp and dipeptides. On the contrary, the selectivity of the PS reaction with peptidoaldehydes with L configuration of the C-terminus residue is totally different from that obtained with simple L-amino aldehydes. It allows us to obtain cis stereoisomers, which cannot be isolated from the reaction with amino aldehydes. But the utility of the peptidoaldehydes as substrates for the PS reaction is reduced by the side formation of enamides which decrease the yield of cyclization. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Vasopressin and nonmammalian hormone vasotocin are known to increase the water permeability of mammalian collecting ducts, frog skin and the urinary bladder. Neurohypophysial nonapeptides have also been shown to interfere with the regulation of renal ion transport. The subject of this study was a search for vasopressin and vasotocin analogues with selective effects on renal water, sodium and potassium excretion. During this study, we synthesised the following peptides: 13 vasotocin analogues modified at positions 4 (Thr or Arg), 7 (Gly or Leu) and 8 ( d-Arg, Lys or Glu); 4 vasopressin analogues modified at positions 4 and 8; and 9 peptides shortened or extended at the C-terminal or with substitutions for Gly-NH2. Most of these peptides had mercaptopropionic acid (Mpa) instead of Cys in position 1. The effects of these nonapeptides on renal water, sodium and potassium transport were evaluated in in vivo experiments using Wistar rats. Some nonapeptides possessed antidiuretic, natriuretic and kaliuretic activities ([Mpa1]-arginine vasotocin, [Mpa1, homoArg8]-vasotocin, [Mpa1, Thr4]-arginine vasotocin and [Mpa1, Arg4]-arginine vasopressin). Substitutions at positions 4 and 8 increased the selectivity of peptide actions. The antidiuretic [ d-Arg8]-vasotocin analogues had no effects on sodium excretion. [Mpa1, Arg4]-arginine vasotocin was antidiuretic and kaliuretic but not natriuretic. [Mpa1, Glu8]-oxytocin had weak natriuretic activity without any effects on water and potassium transport. In accordance with the data obtained, synthesised vasotocin analogues could be good candidates for pharmaceuticals selectively regulating renal sodium and potassium transport, which is of clinical importance. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

No abstract is available for this article. [ABSTRACT FROM AUTHOR]

Short alphahelical peptide sequences were stabilized through Glaser‐Hay couplings of propargylated l‐ and/or d‐serine residues at positions i and i+7. NMR analysis confirmed a full stabilization of the helical structure when a d‐Ser (i), l‐Ser (i+7) combination was applied. In case two l‐Ser residues were involved in the cyclization, the helical conformation is disrupted outside the peptide's macrocycle. [ABSTRACT FROM AUTHOR]