Aspartamide formation

The 20-mer peptide prepared also contained an Asp-Gly sequence, this potentially leading to aspartamide formation, another well documented potential side reaction when performing peptide synthesis. This sequence-dependent side reaction occurs during the Fmoc deprotection step of Asp-containing peptides where the adjacent residue is Gly, Asn, Ser, or Ala. Each subsequent deprotection after the inclusion of Asp will result in an iterative decrease in the peptide purity. In the initial synthesis of the test peptide, deprotection with 20% piperidine at 80 °C led to considerable amounts of aspartimide formation. Addition of 0.1 M HOBt to the deprotection mixture together with piperidine reduced the aspartimide formation and resulted in a 10% increase in crude purity. The use of piperazine in place of piperidine resulted in an even further decrease in the aspartimide formation, and no deletion products were observed despite the decreased pKa of the deprotection reagent. 

The use of PNZ derivatives in conjunction with Fmoc chemistry results in fewer problems with aspartamide and diketopiperazine formation and it is superior to the use of the Alloc group for ornithine and lysine protection in Fmoc based peptide synthesis."... 

Kataoka et al. [57, 58] investigated the formation of polyion complexes (PIC) from a pair of oppositely charged polypeptide block copolymers, namely of anionic poly(ethylene oxide)-( foc -poly(a, P-aspartate) and cationic polyethylene oxide)- foc -poly([2-aminoalkyl]-a,P-aspartamide) (see structure in Fig. 14a), in an aqueous milieu. Mixing of the double-hydrophilic copolymers at an equimolar... 

Aminolysis of the intact rings with taurine leads to the formation of poly(2-sulfoethyl aspartamide) silica and the reaction with ethanolamine to the formation of poly(2-hydroxyethyl aspartamide) silica. Poly(succinimide)-based silica phases are manufactured by PolyLC (Columbia, MD, USA) under the trade names of PolyCAT A for poly(aspartic acid) silica, PolySulfoethyl A for poly(2-sulfoethyl aspartamide) silica, and PolyHydroxyethyl A for poly(2-hydroxyethyl aspartamide) silica. All three poly(succinimide)-based columns have a pore size of 200 A and a surface area of 188 m /g. Various poly(succinimide)-based columns have been used for the separation of carbohydrates, phosphorylated and nonphosphorylated amino acids, petides and glycopeptides, oligonucleotides, and various other polar analytes under HILIC conditions, but lately lost some of their momentum due to a lower chromatographic efficiency in comparison to more modern HILIC phases and column bleed [44]. 

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