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

Renin inhibitors containing psi[CH2O] pseudopeptide inserts.

R E TenBrink1, D T Pals, D W Harris

  • 1Cardiovascular Diseases Research, Upjohn Company, Kalamazoo, Michigan 49001.

Journal of Medicinal Chemistry
|March 1, 1988
PubMed
Summary

Novel renin inhibitors were developed, showing potency comparable to the D-Lys renin inhibitory peptide (RIP). Specific modifications, including N-terminal Boc-protection and unique P4-P3 substitutions, yielded highly effective renin inhibitors for potential therapeutic applications.

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

Review: Implantation and placentation in ruminants.

Animal : an international journal of animal bioscience·2023
Same author

Western Iowa Veterinary Medical Association.

The Journal of comparative medicine and veterinary archives·2022
Same author

Western Iowa Veterinary Medical Association.

The Journal of comparative medicine and veterinary archives·2022
Same author

The Technique of the Tuberculin Test.

The Journal of comparative medicine and veterinary archives·2022
Same author

Practical Antisepsis in Surgery.

The Journal of comparative medicine and veterinary archives·2022
Same author

MRI-Based Deep Learning Segmentation and Radiomics of Sarcoma in Mice.

Tomography (Ann Arbor, Mich.)·2020

Area of Science:

  • Medicinal Chemistry
  • Biochemistry
  • Pharmacology

Background:

  • Renin is a key enzyme in the renin-angiotensin-aldosterone system (RAAS), regulating blood pressure.
  • Inhibiting renin offers a therapeutic strategy for managing hypertension and related cardiovascular diseases.
  • Development of potent and selective renin inhibitors is crucial for RAAS-targeted therapies.

Purpose of the Study:

  • To design and synthesize novel renin inhibitors based on a D-Lys renin inhibitory peptide (RIP) scaffold.
  • To investigate the structure-activity relationships (SAR) of modified renin inhibitors, focusing on P1-P1' and P4-P3 positions.
  • To evaluate the inhibitory potency of newly synthesized compounds against renin activity.

Main Methods:

  • Peptide synthesis and modification, incorporating non-hydrolyzable transition-state isosteres (psi[CH2O]) at critical positions.

Related Experiment Videos

  • Chemical synthesis of N-terminal Boc-protected renin inhibitors with specific amino acid substitutions.
  • Enzyme inhibition assays to determine the IC50 values of the synthesized compounds against human renin.

    • Main Results:

    • Renin inhibitors 2-4, featuring Leu psi[CH2O]Ala, Leu psi[CH2O]Val, and Leu psi[CH2O]Leu at the P1-P1' site, demonstrated potency comparable to the parent RIP.
    • N-terminal Boc-protected inhibitors with Pro psi[CH2O]Phe at P4-P3 positions exhibited significant renin inhibitory activity.
    • Compound 17 (Boc-Phe-Pro psi[CH2O]Phe-His-Leu psi[CH(OH)CH2]Val-Ile-(2-aminomethyl) pyridine) showed a potent IC50 of 1.6 x 10(-9) M.

    Conclusions:

    • The incorporation of specific modifications, such as Leu psi[CH2O]Xaa at P1-P1' and Boc-Pro psi[CH2O]Phe at P4-P3, enhances renin inhibitory potency.
    • The synthesized compounds represent promising leads for the development of novel antihypertensive agents.
    • Further optimization of these renin inhibitors could lead to clinically viable therapeutic options.