Amino group chemical modification

Nearly every protein in a cell is chemically modified after its synthesis on a ribosome. Such modifications, which may alter the activity, life span, or cellular location of proteins, entail the linkage of a chemical group to the free -NH2 or -COOH group at either end of a protein or to a reactive side-chain group in an internal residue. Although cells use the 20 amino acids shown in Figure 2-13 to synthesize proteins, analysis of cellular proteins reveals that they contain upward of 100 different amino acids. Chemical modifications after synthesis account for this difference. 

Wang et al. [135] prepared a novel ABB monomer (1-14, Scheme 8), namely 4-[4-(2,4-diaminophenoxy)phenoxy] phfhalic acid 2-methyl ester, which was polymerized to form the precursor polyamic acid monomethyl ester. The direct polycondensation of the ABB monomer was carried out to form polyamic acid monomethyl ester as a precursor and had a M of 12,000 Da. Chemical imidization in the presence of acetic anhydride and pyridine gave hb-PIs with low DB. The DB of the precursor, as determined by the H NMR spectra, was only 7%. They ascribed the low DB to the differences in the reactivities of the amino groups. End modification reactiOTis were accomplished with acetyl chloride, benzoyl chloride, and phthalic anhydride to form end-capped polyimides. The end-group-modified polyimides were soluble in polar aprotic solvents such as DMSO, DMF, and NMP. TGA measurements showed Ta,s% in the range of 400-520°C, and Tg of 200-258°C. The hb-PIs showed film-forming ability, but they were more brittle than analogous linear polymers. 

Reactions. Although carbapenems are extremely sensitive to many reaction conditions, a wide variety of chemical modifications have been carried out. Many derivatives of the amino, hydroxy, and carboxy group of thienamycin (2) have been prepared primarily to study stmcture—activity relationships (24). The most interesting class of A/-derivatives are the amidines which are usually obtained in good yield by reaction of thienamycin with an imidate ester at pH 8.3. Introduction of this basic but less nucleophilic moiety maintains or improves the potency of the natural material while greatiy increasing the chemical stabiUty. Thus /V-formimidoyl thienamycin [64221-86-9] (MK 0787) (18), C 2H yN204S, (25) was chosen for clinical evaluation and... 

Chemical Modification. The chemistry and synthetic strategies used in the commercial synthesis of cephalosporins have been reviewed (87) and can be broadly divided into ( /) Selection of starting material penicillin precursors must be rearranged to the cephalosporin nucleus (2) cleavage of the acyl side chain of the precursor (2) synthesis of the C-7 and C-3 side-chain precursors (4) acylation of the C-7 amino function to introduce the desked acylamino side chain (5) kitroduction of the C-3 substituent and 6) protection and/or activation of functional groups that may be requked. 

It is extraordinary that eIF4A was found among a number of other proteins bound to the PatA beads without the knowledge of how much PatA is attached to the beads and, more importantly, whether such attachment would lead to inactivation of PatA. In retrospect, it is fortuitous that the amino group used to immobilize PatA onto solid phase can indeed tolerate further chemical modifications without a significant loss of activity. 

GC-C-IRMS instrumentation enables the compound-specific isotope analysis of individual organic compounds, for example, n-alkanes, fatty acids, sterols and amino acids, extracted and purified from bulk organic materials. The principle caveat of compound-specific work is the requirement for chemical modification, or derivatisation, of compounds containing polar functional groups primarily to enhance their volatility prior to introduction to the GC-C-IRMS instrument. Figure 14.7 summarises the most commonly employed procedures for derivatisation of polar, nonvolatile compounds for compound-specific stable isotope analysis using GC-C-IRMS. 

Cysteine is the most frequently used residue for selective chemical modification of proteins due to its relatively low abundance in proteins and the increased nucleophilicity of the thiol group relative to other natural amino acid side chains. The intrinsic selectivity is low unless no cysteine is present or unless all unwanted cysteines... 

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