Structural modification of receptor-binding technetium-99m complexes in order to improve brain uptake

1997 ◽  
Vol 24 (3) ◽  
pp. 316-319 ◽  
Author(s):  
Bernd Johannsen ◽  
Ralf Berger ◽  
Peter Brust ◽  
Hans-Juergen Pietzsch ◽  
Matthias Scheunemann ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Structural Modification ◽  
Brain Uptake ◽  
Technetium 99M

Structural modification of receptor-binding technetium-99m complexes in order to improve brain uptake

1997 ◽  
Vol 24 (3) ◽  
pp. 316-319
Author(s):  
Bernd Johannsen ◽  
Ralf Berger ◽  
Peter Brust ◽  
Hans-Juergen Pietzsch ◽  
Matthias Scheunemann ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Structural Modification ◽  
Brain Uptake ◽  
Technetium 99M

Ketanserin Analogs: The Effect of Structural Modification on 5-HT2 Serotonin Receptor Binding

1995 ◽  
Vol 38 (7) ◽  
pp. 1196-1202 ◽  
Author(s):  
Abd M. Ismaiel ◽  
Kim Arruda ◽  
Milt Teitler ◽  
Richard A. Glennon
Keyword(s):  
Receptor Binding ◽  
Structural Modification ◽  
Serotonin Receptor ◽  
Serotonin Receptor Binding

Somatostatin Receptor-Binding Peptides Labeled with Technetium-99m:  Chemistry and Initial Biological Studies

1996 ◽  
Vol 39 (7) ◽  
pp. 1361-1371 ◽  
Author(s):  
Daniel A. Pearson ◽  
John Lister-James ◽  
William J. McBride ◽  
David M. Wilson ◽  
Lawrence J. Martel ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Somatostatin Receptor ◽  
Technetium 99M ◽  
Biological Studies ◽  
Binding Peptides

scholarly journals Nanobody mediated neutralization reveals an Achilles heel for norovirus

2020 ◽  
Author(s):  
Anna D. Koromyslova ◽  
Jessica Michelle Devant ◽  
Turgay Kilic ◽  
Charles D. Sabin ◽  
Virginie Malak ◽  
...  
Keyword(s):  
Cell Culture ◽  
Binding Site ◽  
Receptor Binding ◽  
Conformational Changes ◽  
Structural Modification ◽  
Cultured Cells ◽  
Murine Norovirus ◽  
Human Norovirus ◽  
Receptor Binding Site ◽  
P Domain

ABSTRACTHuman norovirus frequently causes outbreaks of acute gastroenteritis. Although discovered more than five decades ago, antiviral development has, until recently, been hampered by the lack of a reliable human norovirus cell culture system. Nevertheless, a lot of pathogenesis studies were accomplished using murine norovirus (MNV), which can be grown routinely in cell culture. In this study, we analysed a sizeable library of Nanobodies that were raised against the murine norovirus virion with the main purpose of developing Nanobody-based inhibitors. We discovered two types of neutralizing Nanobodies and analysed the inhibition mechanisms using X-ray crystallography, cryo-EM, and cell culture techniques. The first type bound on the top region of the protruding (P) domain. Interestingly, the Nanobody binding region closely overlapped the MNV receptor-binding site and collectively shared numerous P domain-binding residues. In addition, we showed that these Nanobodies competed with the soluble receptor and this action blocked virion attachment to cultured cells. The second type bound at a dimeric interface on the lower side of the P dimer. We discovered that these Nanobodies disrupted a structural change in the capsid associated with binding co-factors (i.e., metal cations/bile acid). Indeed, we found that capsids underwent major conformational changes following addition of Mg2+ or Ca2+. Ultimately, these Nanobodies directly obstructed a structural modification reserved for a post-receptor attachment stage. Altogether, our new data show that Nanobody-based inhibition could occur by blocking functional and structural capsid properties.AUTHOR SUMMARYThis research discovered and analysed two different types of MNV neutralizing Nanobodies. The top-binding Nanobodies sterically inhibited the receptor-binding site, whereas the dimeric-binding Nanobodies interfered with a structural modification associated with co-factor binding. Moreover, we found that the capsid contained a number of vulnerable regions that were essential for viral replication. In fact, the capsid appeared to be organized in a state of flux, which could be important for co-factor/receptor binding functions. Blocking these capsid-binding events with Nanobodies directly inhibited essential capsid functions. Moreover, a number of MNV-specific Nanobody binding epitopes were comparable to human norovirus-specific Nanobody inhibitors. Therefore, this additional structural and inhibition information could be further exploited in the development of human norovirus antivirals.

Brain uptake and receptor binding of two [11C]labelled selective high affinity NK1-antagonists, GR203040 and GR205171 — PET studies in rhesus monkey

2000 ◽  
Vol 39 (4) ◽  
pp. 664-670 ◽  
Author(s):  
M Bergström ◽  
K.-J Fasth ◽  
G Kilpatrick ◽  
P Ward ◽  
K.M Cable ◽  
...  
Keyword(s):  
Rhesus Monkey ◽  
Receptor Binding ◽  
Brain Uptake ◽  
High Affinity

Kinetics, brain uptake, and receptor binding characteristics of flurazepam and its metabolites

1988 ◽  
Vol 94 (3) ◽  
Author(s):  
LawrenceG. Miller ◽  
DavidJ. Greenblatt ◽  
DarrellR. Abernethy ◽  
H. Friedman ◽  
MyDo Luu ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Brain Uptake ◽  
Binding Characteristics

Synthesis and Preliminary Pharmacological Evaluation of 4´-Arylmethyl Analogues of Clozapine. I. The Effect of Aromatic Substituents

2002 ◽  
Vol 55 (9) ◽  
pp. 565 ◽  
Author(s):  
B. Capuano ◽  
I. T. Crosby ◽  
E. J. Lloyd ◽  
D. A. Taylor
Keyword(s):  
Chemical Synthesis ◽  
Atypical Antipsychotic ◽  
Receptor Binding ◽  
Structural Characterization ◽  
Research Program ◽  
Structural Modification ◽  
Antagonist Activity ◽  
Pharmacological Evaluation ◽  
Binding Data ◽  
Positional Effects

As part of a research program to develop compounds with mixed dopamine D4 and serotonin 5-HT2A antagonist activity with potential for the treatment of schizophrenia, we report a family of compounds based on structural modification of the atypical antipsychotic, clozapine (2). The chemical synthesis, structural characterization and pharmacological evaluation of a series 4�-arylmethyl analogues of clozapine are described. Preliminary receptor binding data are presented, examining primarily the electronic and positional effects of substituents on the introduced arylmethyl group, and secondarily the nature of the aryl ring.

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