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

Conserved Binding Sites01:49

Conserved Binding Sites

5.2K
Many proteins’ biological role depends on their interactions with their ligands, small molecules that bind to specific locations on the protein known as ligand-binding sites. Ligand-binding sites are often conserved among homologous proteins as these sites are critical for protein function.
Binding sites are often located in large pockets, and if their location on a protein’s surface is unknown, it can be predicted using various approaches. The energetic method computationally...
5.2K
Peptide Bonds02:43

Peptide Bonds

84.1K
A peptide bond covalently attaches amino acids through a dehydration reaction. One amino acid's carboxyl group and another amino acid's amino group combine, releasing a water molecule. The resulting bond is the peptide bond. The products that such linkages form are peptides. As more amino acids join this growing chain, the resulting chain is a polypeptide. Each polypeptide has a free amino group at one end. This end has the N-terminal, or the amino-terminal, and the other end has a free...
84.1K
Noncovalent Attractions in Biomolecules02:35

Noncovalent Attractions in Biomolecules

65.6K
Noncovalent attractions are associations within and between molecules that influence the shape and structural stability of complexes. These interactions differ from covalent bonding in that they do not involve sharing of electrons.
Four types of noncovalent interactions are hydrogen bonds, van der Waals forces, ionic bonds, and hydrophobic interactions.
Hydrogen bonding results from the electrostatic attraction of a hydrogen atom covalently bonded to a strong-electronegative atom like oxygen,...
65.6K
Protein Organization01:24

Protein Organization

9.7K
Proteins are polymers of amino acid residues. They are versatile and responsible for different cellular functions, including DNA replication, molecular transport, catalysis, and structural support. Proteins have a hierarchical structure comprising at least three levels of organization: primary, secondary, and tertiary structure. Some large proteins have a quaternary structure where individual protein subunits are linked together.
The primary structure of a protein is its amino acid sequence....
9.7K
Ligand Binding Sites02:40

Ligand Binding Sites

15.4K
Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...
15.4K
Lipids as Anchors01:32

Lipids as Anchors

7.7K
In the plasma membrane, the lipids forming the bilayer can also act as an anchor to tether proteins to the membrane. The three main types of lipid anchors found in eukaryotes are – prenyl groups, fatty acyl groups, and glycosylphosphatidylinositol or GPI groups. Prenyl and fatty acyl groups act as anchors on the cytosolic surface of the membrane, whereas GPI anchors proteins on the extracellular side.
The carboxy-terminal of most of the prenylated proteins, such as Ras proteins, contains...
7.7K

You might also read

Related Articles

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

Sort by
Same author

<i>De novo</i> grafted coiled-coil peptides as p53/<i>h</i>DM2 inhibitors.

RSC chemical biology·2026
Same author

Modular Rh-Catalyzed Synthesis and Biological Profiling of Diverse Pentafluorobenzenesulfonamide Reactive Fragments.

Chemistry (Weinheim an der Bergstrasse, Germany)·2026
Same author

Discovery of SHANK1-PDZ Peptide-Fragment Inhibitors Using a Dynamic Ligation Screening Strategy.

Biochemistry·2026
Same author

Identification of cellular ion channels that facilitate Hazara nairovirus infection enables selection of clinically approved compounds with anti-nairoviral properties.

Scientific reports·2026
Same author

High-throughput discovery and characterisation of pentafluorobenzene sulfonamide modifiers of Aurora A kinase.

RSC chemical biology·2026
Same author

Covalent Peptide-Based N-Myc/Aurora-A Inhibitors Bearing Sulfonyl Fluoride Warheads.

Journal of peptide science : an official publication of the European Peptide Society·2026

Related Experiment Video

Updated: Feb 21, 2026

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors
10:33

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors

Published on: October 26, 2015

11.9K

Hydrocarbon constrained peptides - understanding preorganisation and binding affinity.

Jennifer A Miles1,2, David J Yeo1,2, Philip Rowell1,3

  • 1School of Chemistry , University of Leeds , Woodhouse Lane , Leeds LS2 9JT , UK .

Chemical Science
|October 4, 2017
PubMed
Summary
This summary is machine-generated.

Constrained peptides targeting protein-protein interactions (PPIs) show increased helical structure but not enhanced potency. Enthalpy-entropy compensation influences drug design for PPIs.

More Related Videos

Author Spotlight: A Computational Approach to Decipher Amino Acid Preferences in Multispecific Protein-Protein Interactions
06:50

Author Spotlight: A Computational Approach to Decipher Amino Acid Preferences in Multispecific Protein-Protein Interactions

Published on: January 26, 2024

2.6K
Formation of Ordered Biomolecular Structures by the Self-assembly of Short Peptides
07:26

Formation of Ordered Biomolecular Structures by the Self-assembly of Short Peptides

Published on: November 21, 2013

13.5K

Related Experiment Videos

Last Updated: Feb 21, 2026

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors
10:33

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors

Published on: October 26, 2015

11.9K
Author Spotlight: A Computational Approach to Decipher Amino Acid Preferences in Multispecific Protein-Protein Interactions
06:50

Author Spotlight: A Computational Approach to Decipher Amino Acid Preferences in Multispecific Protein-Protein Interactions

Published on: January 26, 2024

2.6K
Formation of Ordered Biomolecular Structures by the Self-assembly of Short Peptides
07:26

Formation of Ordered Biomolecular Structures by the Self-assembly of Short Peptides

Published on: November 21, 2013

13.5K

Area of Science:

  • Medicinal Chemistry
  • Structural Biology
  • Biophysics

Background:

  • Peptide-based drug discovery faces challenges with protein-protein interactions (PPIs).
  • Constrained peptides offer a strategy to develop probes and drug candidates for PPIs.
  • BH3-family peptides are crucial in regulating apoptosis via PPIs.

Purpose of the Study:

  • To synthesize and evaluate hydrocarbon-constrained BH3-family peptides (BIM and BID) using a novel amino acid.
  • To investigate the impact of conformational constraints on peptide structure, stability, and inhibitory potency against Bcl-xL and Mcl-1.
  • To elucidate the binding mechanism and thermodynamic basis of interaction for constrained peptides.

Main Methods:

  • Synthesis of novel α-alkenylglycine derived amino acids.
  • Preparation of hydrocarbon-constrained BH3-family peptide sequences (BIM and BID).
  • Biophysical analyses (e.g., Circular Dichroism) to assess helical population.
  • Surface Plasmon Resonance (SPR) for binding kinetics and mechanism.
  • X-ray crystallography for structural determination of peptide-protein complexes.

Main Results:

  • Constrained peptides exhibited an increased population of the bioactive α-helical conformation in solution.
  • No significant enhancement in inhibitory potency against pro-apoptotic Bcl-xL and Mcl-1 PPIs was observed.
  • SPR data suggested an induced fit binding mechanism.
  • X-ray analysis confirmed that key helical interactions with the target proteins remained undisturbed.
  • Enthalpy-entropy compensation was identified as the underlying thermodynamic behavior.

Conclusions:

  • Conformational preorganization via hydrocarbon constraints does not necessarily translate to enhanced inhibitory potency for these BH3 peptides.
  • The observed enthalpy-entropy compensation impacts the binding thermodynamics and needs consideration in designing preorganized peptides.
  • Findings have implications for the rational design of peptide therapeutics targeting challenging PPIs.