Peptides have now become important components in pharmaceutical products and are being produced on a large scale. These peptides are bioactive substances responsible for various cellular functions in living organisms. Peptide modification is an important means to change the backbone structure and side chain groups of peptide chains, thereby affecting the physicochemical properties of peptide compounds. The role of such modifications in improving the effective utilization of peptides in vivo is becoming more and more significant. A large number of experiments have shown that modified peptide drugs can significantly reduce the immunogenicity, reduce side effects, improve water solubility, prolong half-life, and change their biodistribution, so as to significantly improve the efficacy of drugs. There are many ways to modify peptides, and a few common modification methods are briefly described below.
1.PEG peptide complex
Currently, monomethoxy polyethylene glycol (mPEG:CH3O2(CH2-CH2O)n2H) is the most widely used type of PEG modification of peptide compounds. This modification method usually involves the introduction of carboxyl groups, amino groups and other active groups at the end of mPEG, or the synthesis of mPEG modified amino acid derivatives, and then linking them with the peptide sequence through solid or liquid phase, so as to achieve the pegylation of the N terminus, C terminus and some amino acid side chains of the polypeptide.
2. Glycopeptides
Glycopeptides, the products of peptides modified by glycosylation, are known as glycopeptides. These glycopeptides play an important role in the study of the structure and function of glycoproteins. Therefore, glycopeptide synthesis is particularly critical. Currently, the connection between oligosaccharides and polypeptide chains is mainly through C, N, O, and S glycosidic linkages, with the N-and O-glycosidic linkages being the most widely used. The chemically unstable nature of glycosidic bonds significantly increases the difficulty of peptide synthesis. “These glycosidic bonds are typically hydrolyzed in an acidic environment, and for all glycosylated serine and threonine derivatives, there is the potential for β-elimination reactions even under slightly alkaline conditions.”
3. Phosphopeptide
Phosphorylation and dephosphorylation of proteins are involved in almost all processes of life activities, including cell proliferation, development, differentiation, neural activity, muscle contraction, metabolism and tumorigenesis. Among them, phosphopeptides are the best models to reflect the structural changes in the phosphorylation process of their parent proteins. According to the amino acid residues that are phosphorylated, phosphorylated peptides can be classified into four classes: N-phosphoylated peptides, O-phosphoylated peptides, acyl phosphopeptides, and S-phosphopeptides. O-phosphoylated peptides are formed by the phosphorylation of a hydroxyl amino acid such as serine, threonine, tyrosine, hydroxyproline or hydroxylysine; N-phosphorylated peptides result from the phosphorylation of arginine, lysine or histidine; Acyl-phosphopeptides are produced by the phosphorylation of aspartate or glutamate; In contrast, S-phosphoylated peptides are formed by the phosphorylation of cysteine.
4. Cyclic peptides
Cyclic peptides can be divided into two types: homocyclic peptides with amino acids linked by amide bonds; The other is heterocyclic peptide, whose structure contains ester bonds, ether bonds, thioester bonds and disulfide bonds in addition to amide bonds.
Shorter linear peptides are readily degraded by a variety of biological enzymes in vivo, and the formation of cyclic peptides can enhance the enzymatic and chemical stability of peptides. Since cyclic peptides have no C and N termini, they can effectively reduce the degradation of aminopeptidase and carboxypeptidase, thereby improving the ability of peptide to resist enzymatic hydrolysis. At the same time, the formation of ring structure limits the conformational change, which may enhance the affinity and selectivity between the peptide and the receptor, improve the activity and reduce the side effects. Therefore, it has become a new direction for new drug development in recent years.
5. Fluorescently modified peptides
Fluorescently labeled peptides combined with imaging techniques can be used to identify specific targets. In vitro imaging using confocal or fluorescence microscopy remains one of the most effective methods for studying multiple biological processes and interactions within cells. These peptides, unlike proteins, localize to specific targets of actin and are not prone to protein aggregation, making them well suited for in vitro tracking. In addition, FITC-labeled cell penetrating peptide (CPP) can also be used to image intracellular components with low cytotoxicity.
For longer sequences, FRET is recommended for their modification. Fluorescence resonance energy transfer (FRET) is a mechanism to describe the energy transfer between two fluorophores. Because FRET efficiency depends in part on the distance between the donor and acceptor molecules, this technique is often used to study enzyme efficiency, protein-protein interactions, or other molecular dynamics.
Post time: May-28-2025