Related Experiment Video
Updated: Jun 25, 2026
07:48
Preparing a 68Ga-labeled Arginine Glycine Aspartate (RGD)-peptide for Angiogenesis
Published on: January 7, 2019
Cyclic DGR-peptidomimetic containing a bicyclic reverse turn inducer as a selective alpha(v)beta (5) integrin ligand
A Trabocchi1, G Menchi, E Danieli
1Dipartimento di Chimica Organica Ugo Schiff, Polo Scientifico di Sesto Fiorentino, Università degli Studi di Firenze, Sesto Fiorentino, Florence, Italy.
Amino Acids
|March 10, 2009
Summary
Researchers developed novel cyclic peptidomimetics using 3-Aza-6,8-dioxabicyclo[3.2.1]octane amino acids. These compounds, including retro-inverso DGR peptides, show micromolar ligand activity for alpha(v)beta(3) and alpha(v)beta(5) integrins.
Area of Science:
- Medicinal Chemistry
- Biochemistry
- Structural Biology
Background:
- Cyclic peptidomimetics are crucial in drug discovery for targeting protein-protein interactions.
- Integrins, such as alpha(v)beta(3) and alpha(v)beta(5), are key targets in various diseases, including cancer and osteoporosis.
- Developing small molecules with high affinity and specificity for integrins remains a significant challenge.
Purpose of the Study:
- To design and synthesize novel cyclic peptidomimetics incorporating 3-Aza-6,8-dioxabicyclo[3.2.1]octane-based amino acids.
- To investigate the binding capabilities of these peptidomimetics towards alpha(v)beta(3) and alpha(v)beta(5) integrins.
- To perform a comparative analysis of RGD and DGR retro-sequences for integrin binding and understand factors influencing preferential binding.
Main Methods:
- Introduction of 3-Aza-6,8-dioxabicyclo[3.2.1]octane-based amino acids into cyclic peptidomimetics.
- Synthesis of cyclic peptides containing RGD or DGR retro-sequences.
- Stereochemical scanning and binding assays to evaluate affinity for alpha(v)beta(3) and alpha(v)beta(5) integrins.
- Conformational analysis of peptidomimetic isomers.
Main Results:
- Retro-inverso DGR peptides were identified as micromolar ligands for alpha(v)beta(3) and alpha(v)beta(5) integrins.
- A comparative analysis revealed differences in binding activity between RGD and DGR containing cyclic peptidomimetics.
- Specific conformational preferences were linked to the preferential binding of compound 4 to the alpha(v)beta(5) integrin.
Conclusions:
- 3-Aza-6,8-dioxabicyclo[3.2.1]octane-based amino acids can effectively induce reverse turns in cyclic peptidomimetics.
- The DGR retro-sequence, when incorporated into these peptidomimetics, yields ligands with notable affinity for integrins.
- Understanding conformational preferences is key to designing selective integrin antagonists.
Related Concept Videos
01:10Integrins
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,...
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,...
01:15Activation of Integrins
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 events provide an effective stimulus.
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 events provide an effective stimulus.
01:30Cancer Vaccines
Cancer treatment vaccines are a rapidly evolving field that offers a promising approach to immunotherapy. Unlike traditional vaccines that prevent diseases, cancer treatment vaccines are designed to treat existing cancers by stimulating the immune system to recognize and attack cancer cells.
Cancer vaccines come in two categories: preventive (prophylactic) and treatment (active). Preventive vaccines, such as the Human Papillomavirus (HPV) vaccine, protect against viruses that cause certain...
Cancer vaccines come in two categories: preventive (prophylactic) and treatment (active). Preventive vaccines, such as the Human Papillomavirus (HPV) vaccine, protect against viruses that cause certain...
01:23Dipeptidyl Peptidase 4 Inhibitors
Dipeptidyl peptidase 4 (DPP-4) is a serine protease widely distributed in the body. It's involved in the inactivation of GLP-1 and GIP hormones, which are crucial for insulin regulation. DPP-4 inhibitors, such as sitagliptin (Januvia), saxagliptin (Onglyza), linagliptin (Tradjenta), alogliptin (Nesina), and vildagliptin (Galvus), help increase the proportion of active GLP-1, enhancing insulin secretion. These inhibitors work by competitively binding to DPP-4. This binding causes a significant...