Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

Cyclic hexapeptide NK-2 antagonists

G Hölzemann1, A Löw, J Harting

  • 1Medical Chemistry Research Department, E. Merck, Darmstadt, Germany.

International Journal of Peptide and Protein Research
|August 1, 1994
PubMed
Summary
This summary is machine-generated.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

How back reaction, hydrogen transport, and capillarity control the performance of hydrogen release from liquid organic carriers.

The Journal of chemical physics·2026
Same author

Performance optimization of bijels as a novel type of catalyst support structure.

Materials horizons·2026
Same author

Simulation of perovskite thin layer crystallization with varying evaporation rates.

Materials horizons·2024
Same author

The interplay of shape and catalyst distribution in the yield of compressible flow microreactors.

The Journal of chemical physics·2024
Same author

Eight weeks of high-intensity interval training versus stretching do not change the psychoneuroendocrine response to a social stress test in emotionally impulsive humans.

European journal of applied physiology·2024
Same author

Patterns in bottlenecks for implementation of health promotion interventions: a cross-sectional observational study on intervention-context interactions in the Netherlands.

Archives of public health = Archives belges de sante publique·2023
Same journal

Structure-activity relationship of the ring portion in backbone-cyclic C-terminal hexapeptide analogs of substance P. NMR and molecular dynamics.

International journal of peptide and protein research·1996
Same journal

Conformation of a water-soluble beta-sheet model peptide. A circular dichroism and Fourier-transform infrared spectroscopic study of double D-amino acid replacements.

International journal of peptide and protein research·1996
Same journal

Application of the allyloxycarbonyl protecting group for the indole of Trp in solid-phase peptide synthesis.

International journal of peptide and protein research·1996
Same journal

NMR solution structure of the receptor binding domain of Pseudomonas aeruginosa pilin strain P1. Identification of a beta-turn.

International journal of peptide and protein research·1996
Same journal

Kinetics of inhibition of aminoacylase activity by dithiothreitol or 2-mercaptoethanol.

International journal of peptide and protein research·1996
Same journal

Alanine scan and N-methyl amide derivatives of Ac-bombesin[7-14]. Development of a proposed binding conformation at the neuromedin B (NMB) and gastrin releasing peptide (GRP) receptors.

International journal of peptide and protein research·1996
See all related articles

Researchers synthesized novel cyclic hexapeptides, some with carbohydrate side chains, demonstrating selective NK-2 receptor antagonism. These compounds show promising binding affinities, highlighting the potential for diverse side chain accommodation without activity loss.

Area of Science:

  • Medicinal Chemistry
  • Peptide Synthesis
  • Pharmacology

Background:

  • Tachykinin receptor antagonists are crucial for treating inflammatory conditions.
  • Cyclic hexapeptides offer a stable scaffold for drug development.
  • NK-2 receptor antagonists are of particular interest for respiratory diseases.

Purpose of the Study:

  • To synthesize and characterize novel cyclic hexapeptides with potential NK-2 receptor antagonist activity.
  • To investigate the impact of carbohydrate side chain moieties on receptor binding.
  • To explore the structural requirements for NK-2 receptor antagonism.

Main Methods:

  • Synthesis of 11 cyclic hexapeptides, including beta-N-glycosylated variants.
  • Coupling of glycosylamine without hydroxyl protecting groups.

Related Experiment Videos

  • Assessment of binding affinity to NK-1 and NK-2 receptors.
  • Determination of antagonist activity using the hamster trachea assay.

    • Main Results:

    • All synthesized peptides exhibited selective NK-2 receptor antagonism.
    • Binding affinities to the NK-2 receptor ranged from 7 x 10(-7) to 1 x 10(-8) M.
    • Most peptides showed low affinity for the NK-1 receptor (IC50 > 10(-5) M).
    • Antagonist activity (pA2-values) ranged from 7.1 to 7.8.
    • The glutamine position accommodates a broad range of side chains without significant activity loss.

    Conclusions:

    • The study successfully synthesized novel cyclic hexapeptides with potent and selective NK-2 receptor antagonist properties.
    • The findings suggest that receptor interaction at the glutamine position is not solely dependent on ionic forces, but also conformational flexibility.
    • These compounds represent promising leads for the development of new therapeutics targeting NK-2 receptor-mediated conditions.