Modification of side chains

Covalent modification of side-chain groups in the Ca -ATPase... 

The selective modification of reactive side chains within proteins with compounds containing NMR-sensitive isotopes offers an alternative route to the labeling of proteins. The chemical modification of side chains with reagents labeled with NMR-sensitive isotopes may permit detailed structural and dynamic questions to be addressed, although perturbations of the system caused by the labeling may be of concern in cases where the chemical identity... 

Numerous modifications of side chains in 1,2,7-thiazepines have been described <1997JME885, 1999JME4054, 2000T9781, 2001JME155, 2002OL4673>. In general, synthetic protocols applicable to alicyclic sulfonamides were successfully used for the manipulation of substituents at the 1,2,7-thiazepine system. Representative examples include microwave-assisted synthesis and Pd-catalyzed amidation reactions have been described <2006T4671>. 

Scheme 2.7.1. Synthesis of the activated carbonate 12 for high-yield modification of side-chain amino groups of diamino acids [15,19],...

A modification (1) of the low high hydrogen fluoride (HF) method (18) is used. Compared to the simpler high only HF procedure, this method reduces modification of side chains, particularly cysteines. 

Paddison, Eikerling and coworkers performed quantum chemical calculations and ab initio MD simulations of crystal hydrates [89-91], The studies reveal the strong influence of the acid functional group on proton mobility at low humidity they show how chemical modifications of side chain entities can make the dissociation of the acid more complete. 

Figure 6.37 shows the two-dimensional structure of cephalosporin C, a compound first isolated from mold cultures of Cephalosporium acremonium in 1948. Cephalosporin C exhibits weak antibacterial effect, but the modification of side chains of the molecule generates cephalosporins having diverse antibacterial activity [105]. Cephalosporins are p-lactam antibiotics, semisynthetically produced from cephalosporin C. 

Modifications of side chain during withanolide formation are shown in Chart X. 

The nonlinear optical properties in solution of selected functionalized PDAs, described herein, have also been evaluated by means of the z-scan technique. Off resonance studies (at 705 nm) show that nonlinear refraction is only comparable to that of the solvent for these dilute solutions, but that nonlinear absorption, characterized by p values, varies significantly, with the nature of the side-chains. O It can be inferred that if bulk films of these PDAs possess suitable nonresonant nonlinear refractive properties for optical devices, modification of side-chain structure can reduce the magnitude of undesirable two photon absorption. 

Interest in porphyrin synthesis continues unabated. The first examples of a truly stepwise procedure, in which four pynole residues are linked together one by one, have now been described (see Section 7). Methods such as this are particularly useful for the preparation of isotopically labeled compounds for biosynthetic studies, where it is of considerable advantage both experimentally and economically to introduce the label as late as possible in the synthetic sequence. It is still, however, often necessary to carry out modification of side chains, or introduce labels, at the porphyrin stage because of the lability of the desired side chains under the conditions required to construct the polypyrrolic precursors and to cyclize them to porphyrins. 

Another effective method for altering physicochemical and biological characteristics of the collagen molecules is the modification of side chains, including succinylation, esterification, and branching of hydrocarbon chains. Such modifications allow the control of electrostatic charge, solubility, interaction with cells and blood, and hydrophilicity. 

Modification of side chain Hydroxyl group a-Amino group... 

Juan AS, Letoumeur D, Izumrudov VA (2(X)7) Quatemized poly(4-vinylpyridme)s as model gene delivery polycations structure-function study by modification of side chain hydrophobicity and degree of alkylation. Bioconjug Chem 18 922-928... 

Synthesis of polymers which undergo radiation-induced modification of side-chain polarity in a catalytic process. 

Fig. 18 Selective modification of side chain secondary alcohol by lipase-catalyzed acylation [150]...

Weinstein et al. (133), and applied to protein 315 (314-136). Bromo-acetyl-V-Dnp-ethylenediamine (BADE) was found to be capable of affinity labeling at least 70% of the active sites of protein 315 with little modification of side chains outside the site. Ninety-six percent of the radioactive affinity label was found in the L chain, where it was localized to tyrosine 34—the same residue that was labeled with Metzger s dia-zonium reagent. The evidence is thus convincing that this tyrosine, located in a hypervariable region, is intimately associated with the Dnp-binding site. 

An attempt to increase the metabolic stabihty of sialosides like 161, for example against mammahan sialidases, led to the corresponding non-carbohydrate mimic 179 (Fig. 6) [83]. Based on manual docking of 161 to a homology model of MAG (Fig. 7a, b), beneficial modifications of side chains in the 2-, 5-, and 9-position of Neu5Ac [28, 72, 73, 81] combined with the replacement of the pyranose core by a cyclohexane ring, the substitution of the 4-OH by an acetamide, and the simplification of the glycerol side chain in the 6-position led to 179 (Fig. 6). 

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