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 Concept Videos

Transducer Mechanism: Enzyme-Linked Receptors01:27

Transducer Mechanism: Enzyme-Linked Receptors

4.9K
Enzyme-linked receptors are cell-surface receptors acting as an enzyme or associating with an enzyme intracellularly. They make excellent drug targets. Drugs can bind to the extracellular ligand-binding domain or directly affect their enzymatic domain and alter their activity.
Major types that are helpful drug targets include:
4.9K
Intracellular Signaling Affects Focal Adhesions01:17

Intracellular Signaling Affects Focal Adhesions

3.8K
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
3.8K
Activation of Integrins01:15

Activation of Integrins

5.6K
Integrins bind ligands and transmit information from outside the cell to inside or vice-versa through an "outside-in signaling" or "inside-out signaling."
In "outside-in signaling," external factors in the extracellular space bind to exposed ligand binding sites on integrins. This causes the inactive protein to undergo a conformational change to become active. Integrins are often clustered on the cell membrane. Repetitive and regularly spaced ligand binding...
5.6K
Treatment for Pulmonary Arterial Hypertension: Endothelin Receptor Antagonists01:18

Treatment for Pulmonary Arterial Hypertension: Endothelin Receptor Antagonists

565
Endothelins (ETs) are potent vasoactive peptides critical in the human body's various physiological and pathological processes. One of the most promising therapeutic strategies for treating pulmonary arterial hypertension (PAH) involves counteracting the effects of these endothelins using a class of drugs known as endothelin receptor antagonists.
ETs are synthesized through a complex sequence of enzymatic steps, primarily involving an enzyme referred to as endothelin-converting enzyme...
565
Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors01:30

Antihypertensive Drugs: Angiotensin-Converting Enzyme Inhibitors

2.8K
Angiotensin-converting enzyme (ACE), a vital component of the renin-angiotensin-aldosterone system, is abundant in lung endothelial cells. ACE converts the inactive decapeptide, angiotensin I, into the active octapeptide, angiotensin II. This potent vasoconstrictor narrows blood vessels, increasing resistance to blood flow and elevating blood pressure. Angiotensin II also stimulates aldosterone production, encouraging kidney cells to reabsorb more sodium and water from urine, thereby increasing...
2.8K
Integrins01:10

Integrins

6.2K
Animal and protozoan cells do not have cell walls to help maintain shape and provide structural stability. Instead, these eukaryotic cells secrete a sticky mass of carbohydrates and proteins into the spaces between adjacent cells. This network of proteins and molecules is called an extracellular matrix or ECM.
Some ECM proteins assemble into a basement membrane to which the remaining components adhere. Proteoglycans typically form the bulk of the ECM while fibrous proteins, like collagen,...
6.2K

You might also read

Related Articles

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

Sort by
Same author

Automated surgical phase recognition and analysis in single-incision laparoscopic cholecystectomy using artificial intelligence.

Surgical endoscopy·2026
Same author

Novel nomogram based on preoperative inflammatory indicators and postoperative clinicopathological features for predicting metachronous liver metastasis of colorectal cancer.

BMC surgery·2026
Same author

Synthesis and characterization of cortinarins - cryptic cyclic peptides from mushrooms of the genus <i>Cortinarius</i>.

Chemical science·2026
Same author

IL-17/IL-17RA Axis Facilitates Immune Evasion in Hepatocellular Carcinoma by Upregulating PD-L1 via the NF-κB Pathway.

Digestive diseases and sciences·2026
Same author

Left atrial strain parameters for predicting new-onset atrial fibrillation: a systematic review and meta-analysis.

Frontiers in cardiovascular medicine·2026
Same author

Structure-based design of Sec61 translocon targeting prodrugs minimize off-target toxicity.

Cell chemical biology·2026

Related Experiment Video

Updated: Apr 7, 2026

Preparing a 68Ga-labeled Arginine Glycine Aspartate RGD-peptide for Angiogenesis
07:48

Preparing a 68Ga-labeled Arginine Glycine Aspartate RGD-peptide for Angiogenesis

Published on: January 7, 2019

7.4K

Ansamer-Controlled Bicyclic Peptides as Integrin αvβ6 Targeting Agents.

Haijian Yang1, Wenyan Dong2, Yana An3

  • 1School of Life Sciences, Fudan University, Shanghai, China.

Angewandte Chemie (International Ed. in English)
|April 5, 2026
PubMed
Summary

Conformational isomers of bicyclic peptides, known as ansamers, show distinct biological activities. The Mansa isomer of a bicyclic RGD peptide selectively inhibits αvβ6 integrin, enabling targeted cancer therapy.

Keywords:
ansamerbicyclic peptidesconformational spaceintegrin αvβ6peptide drug conjugates

More Related Videos

Modification and Functionalization of the Guanidine Group by Tailor-made Precursors
09:45

Modification and Functionalization of the Guanidine Group by Tailor-made Precursors

Published on: April 27, 2017

11.3K
Author Spotlight: Development of a Method for Identifying Small Molecular Antagonists of &#946;2 Integrin Activation
04:15

Author Spotlight: Development of a Method for Identifying Small Molecular Antagonists of β2 Integrin Activation

Published on: February 2, 2024

2.5K

Related Experiment Videos

Last Updated: Apr 7, 2026

Preparing a 68Ga-labeled Arginine Glycine Aspartate RGD-peptide for Angiogenesis
07:48

Preparing a 68Ga-labeled Arginine Glycine Aspartate RGD-peptide for Angiogenesis

Published on: January 7, 2019

7.4K
Modification and Functionalization of the Guanidine Group by Tailor-made Precursors
09:45

Modification and Functionalization of the Guanidine Group by Tailor-made Precursors

Published on: April 27, 2017

11.3K
Author Spotlight: Development of a Method for Identifying Small Molecular Antagonists of &#946;2 Integrin Activation
04:15

Author Spotlight: Development of a Method for Identifying Small Molecular Antagonists of β2 Integrin Activation

Published on: February 2, 2024

2.5K

Area of Science:

  • Medicinal Chemistry
  • Structural Biology
  • Oncology

Background:

  • Bicyclic peptides offer structural rigidity and target specificity, making them suitable for peptide-drug conjugates.
  • Ansamers are non-interconvertible conformational isomers of certain peptides, expanding molecular diversity.
  • Understanding ansamer activity is crucial for developing novel therapeutics.

Purpose of the Study:

  • To investigate the differential biological activities of Pansa and Mansa isomers of a bicyclic peptide incorporating the RGD motif.
  • To assess the inhibitory potential of these ansamers against various integrins, particularly αvβ6.
  • To explore the therapeutic applications of the potent ansamer isomer in cancer treatment.

Main Methods:

  • Synthesis and separation of Pansa and Mansa isomers of a bicyclic RGD peptide.
  • Systematic assessment of inhibitory activities against multiple integrins.
  • Cryo-electron microscopy (cryo-EM) for structural determination of the αvβ6-10-Mansa complex.
  • In vitro cellular internalization and in vivo tumor enrichment studies.
  • Evaluation of a toxin-drug conjugate in a preclinical cancer model.

Main Results:

  • The 10-Mansa isomer demonstrated potent and selective inhibition of the αvβ6 integrin, while the 10-Pansa isomer showed no significant activity.
  • Cryo-EM revealed the specific binding conformation of 10-Mansa to αvβ6, involving hydrophobic interactions and the β6 SDL2 loop.
  • 10-Mansa exhibited enhanced cellular uptake and prolonged tumor tissue enrichment compared to a linear RGD peptide.
  • A 10-Mansa-based toxin-drug conjugate displayed significant in vivo tumor suppression.

Conclusions:

  • Conformational isomerism in ansamers significantly dictates biological activity and target specificity.
  • The αvβ6-selective ansamer 10-Mansa is a promising scaffold for targeted cancer therapies and drug delivery systems.
  • This study highlights the potential of ansamers for discovering novel bioactive molecules and developing effective cancer treatments.