Conjugation of Polymers with Biomolecules and Polymeric Vaccine Development Technologies
Mesut Karahan in Synthetic Peptide Vaccine Models, 2021
In the covalent bonding method the peptide protein is the most preferred carbodiimide of direct cross-linking reagents used to form protein-protein conjugates. The carbodiimides, in which water-soluble and insoluble forms exist, mediate the binding of the carboxylate and primary amines with the amide bond, and the phosphamide bond of the phosphate and amino groups. The water-soluble carbodiimides are more preferred in biochemical conjugates because many macromolecules of biological origin are soluble in aqueous buffer solutions. Carbodiimides which are insoluble in water are generally used in peptide synthesis and in bioconjugation reactions where the molecules must be dissolved only in organic solvents. Products and byproducts that occur in these reactions can only be dissolved in organic solvents and are not soluble in water (Hermanson 1996; McCarthy et al. 2014) (Figure 5.5).The activation carboxyl group of polymers, and coupling with the peptide to obtain a polymer-peptide conjugate with [1-Ethyl-3- (3-dimethylaminopropyl)] EDC method (Mansuroğlu and Mustafaeva 2012).
The Modification Of Carboxyl Groups
Roger L. Lundblad in Chemical Reagents for Protein Modification, 2020
Gilles et al.35 have recently reported studies on the stability of water-soluble carbodiimides in aqueous solution. Carbodiimide concentration was measured spectrophotometrically by reaction with dimethylbarbituric acid. In 50 mM MES buffer/25°C, l-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) has a t1/2 of 37 h (pH 7.0), 20 h (pH 6.0), and 3.9 h (pH 5.0). The addition of 10 mM inorganic phosphate decreases the t1/2 to 3.7 h at pH 7.0 while 100 mM glycine methyl ester decreases the t1/2 to 15.83 (also at pH 7.0). The addition of 100 mM hydroxylamine at pH 7.0 decreases the t1/2 to 0.39 h. l-Ethyl-3-(4-azonia-4,4-dimethylethylpentyl) carbodiimide is approximately one order of magnitude less stable under the same reaction conditions. An effect of phosphate buffers on the modification of phosphorylase by EDC was reported by Takagi et al.36 The inactivation reaction proceeded effectively in N,N,N,’N’-tetramethylethylenediamine buffer at pH 6.2 but very poorly in the presence of glycerophosphate buffer or with phosphate buffer. These results were interpreted as reflecting a specific interaction between phosphate compounds and phosphorylase.
Study of FA12 peptide-modified PEGylated liposomal doxorubicin (PLD) as an effective ligand to target Muc1 in mice bearing C26 colon carcinoma: in silico, in vitro, and in vivo study
Published in Expert Opinion on Drug Delivery, 2022
Atefeh Biabangard, Ahmad Asoodeh, Mahmoud Reza Jaafari, Mohammad Mashreghi
Four peptides were chosen from our peptide bank randomly [20], which were chemically synthesized by GL Biochem (Shanghai, China) with 95% purity. DSPE-PEG2000-COOH (1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[carboxy(polyethylene glycol)-2000]) was purchased from Avanti Polar Lipids (Alabaster, AL). Isopropanol and chloroform were purchased from Merck (Darmstadt, Germany). MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide was also purchased from Sigma-Aldrich (Germany). Commercially available PLD, Doxil, was acquired from Behestan Darou Company (Tehran, Iran). N-hydroxysuccinimide (Sulfo-NHS; ≥98%) and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC; ≥99.0%) were obtained from Merck KGaA (Darmstadt, Germany). RPMI 1640 culture media and fetal bovine serum (FBS) were obtained from Gibco (Carlsbad, CA).
New generation of viral nanoparticles for targeted drug delivery in cancer therapy
Published in Journal of Drug Targeting, 2022
Nikta Alvandi, Maryam Rajabnejad, Zeynab Taghvaei, Neda Esfandiari
There are some linkers for VLPs conjugation categorised in carbodiimide chemistry. DCC (dicyclohexyl carbodiimide) is one of the first and frequented carbodiimides particularly in organic synthesis applications developed as a reagent. Usually, DCC is used for the formation of amide and ester bonds between water insoluble compounds or solid-phase peptide synthesis (Figure 5(E)). Another water-insoluble amide bond-forming agent is DIC (diisopropyl carbodiimide) which has some upsides over DCC, such as being liquid at room temperature and easier dispense than DCC (Figure 5(F)). EDC (1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide) is another water-soluble carbodiimide reagent used in multitudes of biochemical processes as a crosslinker. Its performance is similar to DCC and DIC (Figure 5(G)). Furthermore, another carbodiimide that is suitable for the chemical probing of RNA structure is CMC (1-cyclohexyl-(2-morpholinoethyl) carbidiimide as the metho-p-toluene sulphonate salt) considered as a water-soluble reagent for peptide synthesis or coupling ligands to carriers (Figure 5(H)) [47].
Layer-by-Layer assembled nano-drug delivery systems for cancer treatment
Published in Drug Delivery, 2021
Xinyi Zhang, Tianying Liang, Qingming Ma
The long-term stability of LbL assembled NDDS is one of the major concerns in vivo, particularly under physiological conditions since most of these multilayers will be disassembled under physiological conditions (Tong et al., 2005; Jia et al., 2011). Cross-linking is an effective way to enhance the long-term stability and tune the properties of the nano-multilayers to survive through harsh physiological conditions including high ionic strength, extreme pH and strong polar organic solvent (Wang et al., 2007). Moreover, cross-linking can effectively manipulate the permeability and mechanical strength of LbL assembled NDDS. One of the representative crosslinking methods is carbodiimide chemistry. Uncross-linked components can be selectively released at higher pH, yielding single component and hydrogel-like NDDS. These NDDS exhibit reversible pH-responsive swelling and shrinking, which can be used for loading and releasing anti-cancer therapeutics (Liu et al., 2019).
Related Knowledge Centers
- Organic Chemistry
- Functional Group
- Maser
- N,N'-Dicyclohexylcarbodiimide
- Peptide Synthesis
- Dimerization
- Polymer
- Hydrolysis
- Carbon Dioxide
- Chirality