Papers by Gunnar Lindeberg
Journal of medicinal chemistry, Jan 5, 2006
A benzodiazepine-based beta-turn mimetic has been designed, synthesized, and incorporated into an... more A benzodiazepine-based beta-turn mimetic has been designed, synthesized, and incorporated into angiotensin II. Comparison of the mimetic with beta-turns in crystallized proteins showed that it most closely resembles a type II beta-turn. The compounds exhibited high to moderate binding affinity for the AT2 receptor, and one also displayed high affinity for the AT1 receptor. Molecular modeling showed that the high-affinity compounds could be incorporated into a previously derived model of AT2 receptor ligands.
Journal of medicinal chemistry, Jan 16, 2005
New benzodiazepine-based gamma-turn mimetics with one or two amino acid side chains were synthesi... more New benzodiazepine-based gamma-turn mimetics with one or two amino acid side chains were synthesized. The gamma-turn mimetics were incorporated into angiotensin II (Ang II) replacing the Val(3)-Tyr(4)-Ile(5) or Tyr(4)-Ile(5) peptide segments. All of the resulting pseudopeptides displayed high AT(2)/AT(1) receptor selectivity and exhibited AT(2) receptor affinity in the low nanomolar range. Molecular modeling was used to investigate whether the compounds binding to the AT(2) receptor could position important structural elements in common areas. A previously described benzodiazepine-based gamma-turn mimetic with high affinity for the AT(2) receptor was also included in the modeling. It was found that the molecules, although being structurally quite different, could adopt the same binding mode/interaction pattern in agreement with the model hypothesis. The pseudopeptides selected for agonist studies were shown to act as AT(2) receptor agonists being able to induce outgrowth of neurite ...
Journal of medicinal chemistry, Jan 12, 2004
Three angiotensin II (Ang II) analogues encompassing a benzodiazepine-based gamma-turn-like scaff... more Three angiotensin II (Ang II) analogues encompassing a benzodiazepine-based gamma-turn-like scaffold have been synthesized. Evaluation of the compounds in a radioligand binding assay showed that they had no affinity to the rat liver AT(1) receptor. However, one of the compounds displayed considerable affinity to the pig uterus AT(2) receptor (K(i) = 3.0 nM) while the other two lacked affinity to this receptor. It was hypothesized that the reason for the inactivity of one of these analogues to the AT(2) receptor was that the guanidino group of the Arg(2) residue and/or the N-terminal end of the pseudopeptide could not interact optimally with the receptor. To investigate this hypothesis, a conformational analysis was performed and a comparison was carried out with the monocyclic methylenedithioether analogue cyclo(S-CH(2)-S)[Cys(3,5)]Ang II which is known to bind with high affinity to the AT(2) receptor (K(i) = 0.62 nM). This comparison showed that, in the compounds with high AT(2) re...
Journal of Medicinal Chemistry, 2011
Peptides, 2008
We have recently identified a specific binding site for the tachykinin peptide substance P (SP) f... more We have recently identified a specific binding site for the tachykinin peptide substance P (SP) fragment SP1–7 in the rat spinal cord. This site appeared very specific for SP1–7 as the binding affinity of this compound highly exceeded those of other SP fragments. We also observed that endomorphin-2 (EM-2) exhibited high potency in displacing SP1–7 from this site. In the
Peptides, 2006
Endomorphin-1 (EM-1) and endomorphin-2 (EM-2) represent two opioid active tetrapeptides with high... more Endomorphin-1 (EM-1) and endomorphin-2 (EM-2) represent two opioid active tetrapeptides with high affinity and selectivity for the μ-opioid (MOP) receptor. Both EM-1 and EM-2 exhibit strong inhibition of pain signals in the central nervous system (CNS). In contrast to these compounds, the undecapeptide substance P (SP) facilitates pain influx in the CNS. SP has been implicated in a number of
Acta Chemica Scandinavica, 1970
Acta Chemica Scandinavica, 1970
Acta chemica Scandinavica, 1970
Acta Chemica Scandinavica, 1970
Biochemistry, 1988
The solution conformation of the antibacterial polypeptide cecropin A from the Cecropia moth is i... more The solution conformation of the antibacterial polypeptide cecropin A from the Cecropia moth is investigated by nuclear magnetic resonance (NMR) spectroscopy under conditions where it adopts a fully ordered structure, as judged by previous circular dichroism studies. By use of a combination of two-dimensional NMR techniques the ¹H NMR spectrum of cecropin A is completely assigned. A set of 243
Acta Chemica Scandinavica, 1970
Nuclear Medicine and Biology, 2014
Tetrahedron Letters, 1996
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Papers by Gunnar Lindeberg