Photoreactive cross-linkers

Reported structures for homobifunctional aryl azides include a biphenyl derivative and a naphthalene derivative (Mikkelsen and Wallach, 1976), a biphenyl derivative containing a central, cleavable disulfide group (Guire, 1976), and a compound containing a central l,3-diamino-2-propanol bridge between phenyl azide rings that are nitrated (Guire, 1976). The only commercially available homobifunctional photoreactive cross-linker is BASED. 

An important class of heterobifunctional reagents is the photoreactive cross-linkers that have one end that can be photolyzed to initiate coupling. Photoreactive cross-... 

Suitable light sources for photolyzing include sunlamps manufactured by a number of companies, such as Philips Ultrapnil MLU 300 W, General Electric Sunlamp RSM 275 W, or National Self-Ballasted BHRF 240-250 V 250 W-P lamp. Irradiation for 15 min with such lamps while the sample is cooled in an ice bath will result in good photolysis of photoreactive cross-linkers and modification reagents. 

Of the following amine-reactive and photoreactive cross-linkers, the overwhelming majority use an aryl azide group as the photosensitive function. Only a few use alternative photoreactive chemical reactions, particularly perfluorinated aryl azide, benzophenone, or diazo compounds. For general background information on photoreactive cross-linkers see Das and Fox (1979), Kiehm and Ji (1977), Vanin and Ji (1981), Meijer et al., 1988), and Brunner (1993). 

Figure 172 SASD is a photoreactive cross-linker that can be used to modify amine-containing compounds through its NHS ester end and subsequently photolyzed to initiate coupling with nucleophiles (after ring expansion to an intermediate dehydroazepine derivative). The cross-links may be selectively cleaved at the internal disulfide group using DTT.

Benzophenone-4-maleimide is a heterobifunctional photoreactive cross-linker that has sulfhydryl reactivity similar to benzophenone-4-iodoacetamide discussed in the... 

Finally, the small amine-reactive and photoreactive cross-linker NHS-ASA (Chapter 5, Section 3.1) can be iodinated to provide a nondeavable radioactive conjugate. 

If the drug lacks a suitable reactive group, sometimes one can be introduced through reduction, oxidation, or disulfide exchange. Photoreactive cross-linkers are also used for compounds that are difficult to conjugate (36). 

Commonly used photoreactive cross-linkers with demonstrated utility in biological settings include benzo-... 

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