Modification of peptidomimetics with minimal local changes has been successful, and various local modification strategies have been developed to improve the stability of peptidomimetics and enhance biological activity. CD BioSciences offers a variety of peptidomimetic local modification solutions to meet basic research, drug discovery and other needs.
Overview of Local Modifications
Altering the local structure of the peptide, although introducing some degree of conformational bias, produces minimal modifications to the original peptide. Such modifications are generally limited to single amino acids and can be divided into local modifications to the backbone and side chains. Changes in single amino acids have been reported to cause extensive changes in peptide structure, such as substitution of carbonyl groups with thiol, methylene, phosphinic and boronic acid groups. The use of unnatural amino acids as building blocks for the development of peptidomimetics has now attracted extensive research interest. Local modifications of peptidomimetics can include α-amino acids bearing modified side chains, rigid cyclic compounds that are isosteres of amino acids, and so on.
Types of Local Modifications
Amide bond surrogates
By introducing amide bond substitutes for modification, they simulate the structural features of the peptide bond and regulate the conformational distribution and hydrogen bonding ability, such as the introduction of sulfonamides and phosphinic.
Side chain modifications
The introduction of local modifications around the side chain regulates the conformational distribution of the peptidomimetic, such as the addition of aromatic amino acids or the introduction of polar appendages to address any polar or hydrogen bond interactions with the target receptor.
Nα-Cα cyclized amino acids
The introduction of cyclic amino acids such as proline analogs aims to modulate the ratio of cis/trans acyl-Pro bonds, constrain the conformation of peptide bonds, and create the ability to generate cis/trans isomerization.
Cα- and N-alkylation of amino acids
The conformational flexibility can be reduced by Cα- and N-alkylation, which can be applied to acyclic or cyclic structures, and α-Me-alanine is the most widely studied a-alkylated amino acid.
Constraining the side chain rotational freedom
The inclusion of rigid elements in the peptidomimetic to reduce the conformational freedom of the side chain through double bonds or cycles; or the introduction of dehydroamino acids can prevent the rotation of Cα-Cβ at the χ dihedral angle.
Our Services
CD BioSciences offers comprehensive local modification services for peptidomimetics.
- Our PepDomTM platform can conduct professional peptidomimetic design based on the specific requirements of customers, and meet the needs of overall structural modification through single changes to the peptidomimetic backbone and side chain amino acids. Whether for the purpose of limiting the degrees of freedom of peptidomimetic chains or for generating special conformations, our PepDomTM can do it.
- Our local modification service of peptidomimetics can be carried out during the development of targeted peptidomimetics and functional peptidomimetics, or the peptidomimetic sequences provided by customers can be redesigned and developed based on the special requirements of the structure.
Features of Our Service
- Variety of Options-Various local modifications are available and can be individually customized according to customer requirements.
- Development Scale-A high-throughput development platform to meet the development needs of customers at various levels.
- Project Cycle-One-stop development process to ensure the fastest delivery.
- Quality Assurance-Strict results verification before delivery to ensure the best quality.
CD BioSciences specializes in providing a variety of services for the development of peptidomimetics. We are committed to providing comprehensive local modification services for peptidomimetics, as long as you are interested in any aspect of peptidomimetic development, please contact us for the best solution.
Reference
- Lenci, E., & Trabocchi, A. (2020). Peptidomimetic toolbox for drug discovery. Chemical Society Reviews, 49(11), 3262–3277.
All of our services are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.
