Amines modification with

Modification of Amine-Dendrimers with Suifo-NHS-LC-SPDP... 

A common choice of crosslinker for this type of reaction is sulfo-SMCC, which has been used extensively for antibody conjugation (Chapter 20, Section 1.1). A better option for dendrimer conjugation is to use a similar crosslinker design, but one that contains a hydrophilic PEG spacer arm to promote dendrimer hydrophilicity after modification. Derivatization of an amine-dendrimer with a NHS-PEG-maleimide can create an intermediate that is coated with water-soluble PEG spacers. This modification helps to mask any potential for nonspecific interactions that the PAMAM surface may have, while providing terminal thiol-reactive maleimides for coupling ligands (Figure 7.10). 

The same type of modification with carboxylate molecules can be done in aqueous solution using EDC. If the ligand to be coupled only has a single carboxylate with no amines or other nucleophiles present, then the dendrimer and ligand may be dissolved at a similar molar ratio in aqueous buffer and EDC added to facilitate the coupling reaction. 

The following protocol for the modification of an amine-dendrimer with an SCN-Bzl-DTPA chelator is based on the literature references previously cited. Dendrimers of other generations will work well in this procedure provided that the molar ratios of reactants are adjusted for the size of dendrimer being used and the substitution level desired. 

Figure 13.4 APTS-modified surfaces may be further derivatized with amine-reactive crosslinkers to create additional surface characteristics and reactivity. Modification with NHS-PEG4-azide forms a hydrophilic PEG spacer terminating in an azido group that can be used in a click chemistry or Staudinger ligation reaction to couple other molecules.

Although amine-reactive protocols, such as SATA thiolation, result in nearly random attachment over the surface of the antibody structure, it has been shown that modification with up to 6 SATAs per antibody molecule typically results in no decrease in antigen binding activity (Duncan et al., 1983). Even higher ratios of SATA to antibody are possible with excellent retention of activity. 

Figure 22.10 Hydroxylic-containing lipid components, such as PG, may be oxidized with sodium periodate to produce aldehyde residues. Modification with amine-containing molecules then may take place using reductive amination.

Dextran derivatives containing carboxyl- or amine-terminal spacer arms may be prepared by a number of techniques. These derivatives are useful for coupling amine- or carboxylate-containing molecules through a carbodiimide-mediated reaction to form an amide bond (Chapter 3, Section 1). Amine-terminal spacers also can be used to create secondary reactive groups by modification with a heterobifunctional crosslinking agent (Chapter 5). 

This type of modification process has been used to form sulfhydryl-reactive dextran polymers by coupling amine spacers with crosslinkers containing an amine reactive end and a thiol-reactive end (Brunswick et al., 1988 Noguchi et al., 1992). The result was a multivalent sulfhydryl-reactive dextran derivative that could couple numerous sulfhydryl-containing molecules per polymer chain. 

A.B. Bourlinos, D. Gournis, D. Petridis, T. Szabo, A. Szeri, I. Dekany, Graphite oxide chemical reduction to graphite and surface modification with primary aliphatic amines and amino acids, Langmuir, 19 (2003) 6050-6055. 

Figure 1.1 Stepwise production of metal-particle multilayer arrays. The attachment ofthe Au or Ag nanoparticles onto ITO-modified glass was achieved by using silanes that have an amine terminus group. This modification step allows for further modification with nanoparticles onto the surface of the ITO. After the nanoparticle attachment a redox-active bridging molecule was...

An additional modification in the above synthetic scheme is possible by introducing the aromatic diamine in the form of its trimethylsilyl derivative [72]. Monotrimethylsilyl-substituted amines are readily prepared from the free amine with hexamethyldisilazane or trimethylsilyl chloride in the presence of a tertiary amine [73, 74] whereas bis(trimethylsilyl)-substituted amines require more aggressive reagents, such as butyllithium in conjunction with trimethylsilyl chloride [75]. As illustrated in Scheme 19, monotrimethylsilyl-substituted amines react with acyl chlorides to form the corresponding amides and liberate trimethylsilyl chloride. Monotrimethylsilyl-substituted amines are reported to display increased reactivity with acyl chlorides [76], This is of great synthetic importance since the increased reactivity allows for reaction with low basicity amines. Bis(trimethylsilyl)-substituted amines, on the other hand, react with acyl chlorides to form the corresponding JV-trimethylsilyl amides, see Scheme 20. The JV-trimethylsilyl amides are much more soluble in common organic solvents. However, they are hydrolytically unstable and readily convert back to the free amides. 

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