Modified peptides are peptides that have undergone chemical alterations or modifications to their structure, amino acid sequence, or properties. These modifications can enhance the peptides’ stability, solubility, bioactivity, or specificity for a particular application. Modified peptides are widely used in biomedical research, diagnostics, and therapeutics.
Types of modified peptides:
Post-Translational Modifications (PTMs):
PTMs are chemical modifications that occur naturally after translation during protein synthesis. Examples of PTMs include phosphorylation, glycosylation, acetylation, methylation, and proteolytic cleavage. These modifications can alter peptide structure, stability, and function, and they play crucial roles in regulating protein activity, localization, and interaction with other molecules.
Non-Natural Amino Acids:
Modified peptides may contain non-natural amino acids, which are amino acid analogs with altered side chains or functional groups. Non-natural amino acids can be incorporated during peptide synthesis to introduce specific chemical functionalities or improve peptide properties. Examples of non-natural amino acids include D-amino acids, amino acids with modified side chains (e.g., fluorinated amino acids, amino acids with bulky or hydrophobic groups), and amino acid derivatives with reactive handles for conjugation or labeling.
Conjugated Peptides:
Conjugated peptides are peptides that have been chemically linked to other molecules, such as fluorophores, biotin, drugs, or nanoparticles, to introduce specific functionalities or enable specific interactions. Conjugation can be achieved through various chemical reactions, including amide coupling, click chemistry, thiol-maleimide chemistry, and bioorthogonal chemistry.
Cyclized Peptides:
Cyclized peptides are peptides that have been covalently cyclized to form a closed-loop structure by linking the N- and C-termini or side chains of amino acids within the peptide sequence. Cyclization enhances peptide stability, resistance to enzymatic degradation, and bioactivity. Cyclized peptides can be synthesized using chemical crosslinking, disulfide bond formation, lactam bridge formation, or other cyclization strategies.
Modified Backbone Structures:
Modified peptides may have altered backbone structures, such as peptidomimetics or peptide mimetics, which mimic the structure and function of natural peptides but contain non-peptide bonds or scaffolds. Peptidomimetics are designed to enhance peptide stability, improve pharmacokinetic properties, or target specific biological pathways. Examples of modified backbone structures include β-peptides, α-peptoids, and peptoids.
What is the production process of modified peptides?
Modified peptide production refers to the process of synthesizing peptides with specific chemical modifications or alterations to their structure or properties. This process typically involves solid-phase peptide synthesis (SPPS) or liquid-phase peptide synthesis (LPPS), followed by post-synthetic modification steps. Here’s an overview of the modified peptide production and modification process:
1. Conjugation:
Conjugation involves attaching functional molecules, such as fluorophores, biotin, or drugs, to peptides to introduce specific properties or enable specific interactions. Common conjugation techniques include amide coupling, click chemistry, and thiol-maleimide chemistry.
2. Labeling:
Labeling peptides with fluorescent dyes, radioactive isotopes, or other detectable tags allows for visualization, quantification, and tracking of peptides in biological systems. Labeling can be achieved through direct conjugation or indirect methods using affinity tags or linkers.
3. Cyclization:
Cyclization involves forming a covalent bond between the N- and C-termini of a peptide to create a cyclic structure. Cyclization enhances peptide stability, resistance to enzymatic degradation, and bioactivity. Cyclization techniques include disulfide bond formation, lactam bridge formation, and click chemistry-mediated cyclization.
4. Structural Modification:
Structural modification of peptides involves altering their amino acid sequence or side chain chemistry to enhance desired properties such as stability, solubility, or bioactivity. Examples of structural modifications include amino acid substitutions, backbone modifications (e.g., peptide backbone cyclization), and post-translational modifications (e.g., phosphorylation, glycosylation).
5. PEGylation:
PEGylation involves attaching polyethylene glycol (PEG) chains to peptides to improve their pharmacokinetic properties, such as stability, solubility, and circulation time in the body. PEGylation can also reduce immunogenicity and proteolytic degradation of peptides.
6. Crosslinking:
Crosslinking peptides involves linking multiple peptide molecules together to form higher-order structures or peptide conjugates. Crosslinking can enhance peptide stability, increase binding affinity, or enable the formation of peptide-based materials for biomedical applications.
7. Functionalization:
Functionalization of peptides involves introducing specific functional groups, such as reactive handles or targeting moieties, to enable site-specific conjugation or interaction with biomolecules or surfaces. Functionalized peptides can be used for targeted drug delivery, imaging, or biomaterials engineering.
Peptide modification is a versatile and powerful approach for tailoring the properties and functionalities of peptides to meet specific research, diagnostic, or therapeutic needs. By leveraging various chemical reactions and modification strategies, researchers can design peptides with enhanced stability, bioactivity, and compatibility for a wide range of applications in biotechnology and medicine.
