Linker hydroxyl

The protocols described in this section are applicable to all linker-derivatized resins in which loading involves esterification of the first amino acid to a linker hydroxyl group. The ease of esterification with Fmoc-amino acids increases in the order 5<3= 4<6<1 =2. 

Displacement of a volatile with a nonvolatile alcohol is an important reaction for curing paint films with amino cross-linkers and amino resias on textile fabrics or paper. FoUowiag is an example of a methoxymethyl group on an amino resia reacting with a hydroxyl group of a polymer chain. 

The diisopropoxy-bis-(triethanolamine)-titanate, TYZORTE [36673-16-2] is an excellent cross-linker for aqueous solutions of hydroxyl-containing polymers. The reaction product of TYZORTPT with a mixture of trialkano1 amines and dialkanolarnines or monoalkano1 amines can be used to cure polyester-based powder coatings (109). Other ligands of this type iaclude triisopropano1 amine [122-20-3] ... 

Polyfunctional 2-hydtoxyalk5iamides can serve as cross-linkers for carboxyHc acid-terrninated polyester or acryHc resins (65). The hydroxyl group is activated by the neighboring amide linkage (66). SoHd grades of hydroxyamides are finding use as cross-linkers for powder coatings (67). 

The synthesis of aldehydes and ketoamides was performed on solid phase as well as in solution (Scheme 2.2). A semicarbazone linker (6) was employed for the assembly of the aldehydes on solid phase whereas the corresponding aminoalcohol was coupled in solution to the tripeptide and oxidized to the aldehyde, which produced epimeric mixtures [137]. For the synthesis of the ketoamides, hydroxyester THP resins were used as solid support ((7), Scheme 2.2) [138]. In solution the peptide bond was formed using an aminohydroxycarboxylic acid building block [138, 147]. Oxidation of the free hydroxyl group yielded the final inhibitors ((8), Scheme 2.2). 

V. RESINS AND LINKERS FOR HYDROXYL AND GENERATION OF AMINO FUNCTION... 

Figure 2.3 SAM surface modification has been done using monothiol and dithiol compounds containing PEG linkers. Useful coatings typically contain mainly PEG-hydroxyl or PEG-monomethyl ether linkers that provide a biocompatible lawn, which prevents nonspecific binding of proteins to the metallic surface. About 10 percent of the surface modifications are done using a longer carboxylate-containing thiol-PEG linker that provides sites for attachment of affinity ligands.

Annunziato, M.E., Patel, U.S., Ranade, M., and Palumbo, P.S. (1993) p-Maleimidophenyl isocyanate A novel heterobifunctional linker for hydroxyl to thiol coupling. Bioconjugate Chem. 4, 212-218. 

Key fsi, solid support and linker P, unique protecting group X, activating group indicates a uniquely differentiated hydroxyl group... 

This loading approach is successful for the relatively unhindered 6-hydroxyl, but proved to be inefficient for more sterically encumbered alcohols. A modification of the abovementioned method has been developed to enable attachments through these more hindered sites.9 This process is accomplished with inexpensive materials, and the linker is compatible with a variety of reaction conditions. Moreover, it allows for facile recycling of the polymer support for further use once the final carbohydrate assemblage is cleaved from the resin. 

FIGURE 5.17 Resins and linkers for synthesis of peptides using Fmoc/tBu chemistry. The linkers are secured to supports by reaction with aminomethyl resins. A protected amino acid is anchored to the support as an ester by reaction with a hydroxyl or chloro group (italicized). The alkoxy and phenyl substituents render the benzyl esters sensitive to the cleavage reagents. 

Trimethylpyridine (collidine) (2) is more basic than pyridine and is recommended as being superior for minimizing enantiomerization of the activated residue during o/inium salt-mediated reactions of protected segments with an amino group and Fmoc-Cys(R)-OH with the hydroxyl group of a linker-resin (see Section 8.10). 

Di-/m-butyl-4-methy I pyridine (3) is hindered, allows coupling of Fmoc-amino-acid fluorides with weak nucleophiles (see Section 7.12) and is best for minimizing the enantiomerizaton of Fmoc-Cys(tBu)-F (see Section 8.1) during its reaction with the hydroxyl group of a linker-resin. 

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