Heterobifunctional

Thus, heterobifunctional cyclohexadienes are accessible from benzene by temporary complexation to Fe2+ which reverses the reactivity of the aromatic. Double nucleophilic attack is possible but only using protection-deprotection by hydride. 

Chitosan is the main structural component of crab and shrimp shells. Chitosan contains both reactive amino and hydroxyl groups, which can be used to chemically alter its properties under mild reaction conditions. Al-acyl chitosans were already reported as blood-compatible materials. UV irradiation grafting technique was utilized to introduce obutyrylchitosan (OBCS) onto the grafted SR film in the presence of the photosensitive heterobifunctional cross-linking agent. The platelet adhesion test revealed that films grafted on OBCS show excellent antiplatelet adhesion. 

Haptens with an amino group. Amine groups in haptens, carrier proteins or both can be modified for conjugation through homo- or heterobifunctional crosslinkers such as acid anhydrides (e.g., succinic anhydride), diacid chlorides (e.g.. 

For the pad-batch fixation of heterobifunctional Cibacron C (Ciba) dyes four alkali variants have been suggested [159] ... 

Table 12.19 Pad liquor formulations and fixation conditions for application of monofunctional and heterobifunctional reactive dyes by three continuous dyeing methods [162]...

The same heterobifunctional initiator, 2-phenyl-2-[(2,2,6,6-tetramethy-piperidino)oxy] ethyl 2-bromo-2-methyl propanoate, was employed for the synthesis of PMMA-fo-PfBuA-fo-PS triblock terpolymers via the combination of ATRP and NMP [136]. Styrene was initially polymerized through the alkoxyamine function in bulk at 125 °C, leading to PS chains with bromine end groups. Subsequent addition of fBuA in the presence of CuBr/PMDETA provided the PS-fr-PfBuA diblock. Further addition of CuCl, to achieve halogen exchange and MMA yielded the desired triblock copolymer with... 

FIG. 70. PAMAM can be modified with varied linkage functionalities thioureas (A) amides (B) heterobifunctional interspacing groups (C) and mixed sugars (D). 

M.-G. Baek and R. Roy, Simultaneous binding of mouse monoclonal antibody and streptavidin to heterobifunctional dendritic L-lysine core bearing T-antigen tumor marker and biotin, Bioorg. Med. Chem., 9 (2001) 3005-3011. 

Fig. 6 Utility of the heterobifunctional PEG. Two different components such as drug and ligand can be introduced at the different ends of PEG...

Fig. 7 Synthesis of heterobifunctional PEG. (a) Nagasaki et al. developed a method for the polymerization of EO using an initiator containing defined functionalities [16, 17]. (b) Akiyama et al. further developed a synthetic route to prepare a series of heterobifunctional PEGs [18-21]. After the ring-opening polymerization of ethylene oxide, a second functional group was introduced at the co-end of PEG...

Fig. 8 Examples of heterobifunctional PEGs popularly used for PEGylation...

To date, a variety of heterobifunctional PEGs have been reported. Some popular derivatives are shown in Fig. 8. Several PEG derivatives are now commercially available from NOF, Japan. 

Nagasaki Y, Iijima M, Kato M, Kataoka K (1995) Primary amino-terminal heterobifunctional poly(ethylene oxide). Facile synthesis of poly(ethylene oxide) with a primary amino group at one end and a hydroxyl group at the other end. Bioconjug Chem 6 702-704... 

Akiyama Y, Otsuka H, Nagasaki Y, Kato M, Kataoka K (2000) Selective synthesis of heterobifunctional poly(ethylene glycol) derivatives containing both mercapto and acetal terminals. Bioconjug Chem 11 947-950... 

Hiki S, Kataoka K (2007) A facile synthesis of azido-terminated heterobifunctional poly (ethylene glycol)s for click conjugation. Bioconjug Chem 18 2191-2196... 

Hiki S, Kataoka K (2010) Versatile and selective synthesis of click chemistry compatible heterobifunctional poly(ethylene glycol)s possessing azide and alkyne functionalities. Bioconjug Chem 21 248-254... 

PEG polymer has to be suitably functionalized at one or both terminals. PEGs that are activated at each terminus with the same reactive moiety are known as homobifunctional. If the functional groups present are different, then the PEG derivative is referred as heterobifunctional or heterofunctional. Chemically activated PEG polymer derivatives are used to attach the PEG to the desired molecule or ligand. 

The heterobifunctional PEGs are very useful in linking two entities in cases where a hydrophilic, flexible, and biocompatible spacer is needed. Preferred end groups for heterobifunctional PEGs are maleimides, vinyl sulfones, pyridyl disulfides, amines, carboxylic acids, and /V-hydroxysuccinimide (NHS) esters. 

The greatest degree of control in crosslinking procedures is afforded using heterobifunctional reagents (Chapter 5). Since a heterobifunctional crosslinker has different reactive groups on either end of the molecule, each side can be directed specifically toward different functional... 

Figure 1.25 Heterobifunctional crosslinking agents used in multi-step protocols result in the best control over the products formed.

Purify the reduced IgG from excess 2-mercaptoethylamine and reaction by-products by dialysis or gel filtration using a desalting resin. All buffers should contain 1-10 mM EDTA to preserve the free sulfhydryls from metal-catalyzed oxidation. The sulfhydryl-containing half antibody now may be used in conjugation protocols that use —SH-reactive heterobifunctional crosslinkers (Chapter 5, Section 1). 

BMPA is N-(3-maleimidopropionic acid (or 3-maleimidopropionic acid), which contains a thiol-reactive maleimide group at one end and a carboxylate group on the other end (Rich et al., 1975 Moroder, 1983, 1987). The compound is the acid precursor to the short, heterobifunctional crosslinker 3-maleimidopropionic acid N-hydroxysuccinimide ester (BMPS). 

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