Iminodiacetic acid linker

Fig- 2. The two-stage release ofpeptides from iminodiacetic acid-based dual cleavable linker. 

The selected example by Seneci et al. [51] reported the use of an IDA-DC [52] (iminoDiacetic acid based double cleavable) linker for structure determination and controlled release of pool libraries based on teicoplanin aglycone (TD) [53] and tested for their antimicrobial activities. The synthesis and the structure of the linker and the structure of teicoplanin aglycone are shown in Figure 9.15. Starting from iminodiacetic acid the linker was prepared in four trivial chemical steps (the cyclic anhydride used in step 4 was prepared in two steps from iminodiacetic acid) its structure was symmetrical with the amide arm bearing the carboxylic handle for the solid support attachment and the identical other arms bearing protected propylamine groups for the library synthesis. 

Iodine (1 M) in THF-2,6-dimethylpyridine-water (40 10 1 v/v/v) (25-fold molar excess) is added and the reaction vessel is mixed for 30 min. After this time, the vessel is drained and the peptide resin is washed with DMF and diethyl ether (three times each) and dried in vacuum. The peptide resin is ready for final cleavage and deprotection. As usual, the scavenger cocktail is dictated by the linker used and the protecting groups present in the sequence. The phosphopeptide is purified by ion-exchange chromatography or preparative HPLC on a reversed-phase colunm. The separation of phosphopeptide from nonphosphorylated impurities can be carried out by affinity chromatography on Fe " Chelex gel (iminodiacetic acid epoxy activated Sepharose 6B) [118]. 

Linker compound—Gly— iminodiacetic-acid- based double compound—Gly —NH cleavable 0 0 0... 

Fig. 3. Some examples of multifunctional organic linker molecules a) lactic acid, b) oxalic acid, c) adipic acid, d) azelaic acid, e) malonamide, f) oxodiacetate, g) iminodiacetate, h) oxypyridine-4-carboxylic acid, i) squaric acid, j) 1,3-benzenedicarboxylic acid, k) 1,3,5-benzenetricarboxylic acid, 1) isonicotinic acid, m) 2,6-pyridine dicarboxyUc acid, n) 3,5-pyrazoledicarboxyUc acid, o) 4,4 -dipyridyl...

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