Unmodified residues

Modification of specific amino acid residues should affect the rate of proteolysis by those enzymes which have specificity for the unmodified residues. For example, modification of the lysine residues of a protein restricts the action of trypsin. Dimethylated casein undergoes a slower rate of hydrolysis by trypsin in vitro, and the extent of proteolysis is lower than that of casein (267). An unexpected finding was that the rate and extent of hydrolysis of dimethylated casein by a-chymotrypsin are also adversely affected, while hydrolysis by subtilisin is not. Peptides derived from dimethylated casein were inhibitory of a-chymotrypsin. 

The unmodified and complementary oligonucleotides were also synthesized, in order to detect thermodynamic and spectroscopic differences between the double helices. Circular dichroism spectra revealed that the covalently bound anthracene does not stack in the centre of the DNA double helix. Mutagenic activity by intercalative binding of the anthracene residue is thus unlikely. Only in vitro and in vivo replication experiments with site-specifically modified... 

An abasic peptide (Ac-Gys -Lys-(Ser-Ala-Ala-Lys)4-Ser-Gly-Lys-NH2) with unmodified Ser residues was synthesized and used as a control. No induced cooperative binding to. TAjGsAsT) was observed in the UV melting curve with this abasic peptide. This indicated that the cooperative melting between aPNA and its complementary DNA was not merely a reflection of nonspecific interactions be-... 

After secretion from the cell, certain lysyl residues of tropoelastin are oxidatively deaminated to aldehydes by lysyl oxidase, the same enzyme involved in this process in collagen. However, the major cross-links formed in elastin are the desmosines, which result from the condensation of three of these lysine-derived aldehydes with an unmodified lysine to form a tetrafunctional cross-hnk unique to elastin. Once cross-linked in its mature, extracellular form, elastin is highly insoluble and extremely stable and has a very low turnover rate. Elastin exhibits a variety of random coil conformations that permit the protein to stretch and subsequently recoil during the performance of its physiologic functions. 

Fig. 3.4f shows an exclusion chromatogram on unmodified silica. The sample is an epoxy resin with an average Mr of 900. Fig. 3.4g shows the determination of pesticide residues in a sample of chicken fat, and is an example of how exclusion can be used to clean up complex samples. First, a pesticide-free sample of the fat is run as a blank, then the blank is spiked with the pesticides to determine their retention volumes. When the sample is injected, the eluent containing the pesticides is collected. The solvent is evaporated, the residue dissolved in acetonitrile and the pesticides are then separated on a reverse phase column. 

The significance of protein oxidation became paramount with the advent of recombinant protein biologies used as human therapeutics. Careful characterization of protein stability is essential to maintaining the efficacy of protein pharmaceuticals. If even a single side chain amino acid residue becomes oxidized, then a protein therapeutic may not have the same activity in vivo as the unmodified protein. 

As anticipated, 33 binds in the desired manner, capturing the thiol by the aldehyde group (Scheme 5). Unexpectedly, 33 binds with only a twofold improved affinity when compared to the parent dipeptide derivative containing the unmodified pTyr residue [137]. 

Union Carbide (34) and in particular Dow adopted the continuous mass polymerization process. Credit goes to Dow (35) for improving the old BASF process in such a way that good quality impact-resistant polystyrenes became accessible. The result was that impact-resistant polystyrene outstripped unmodified crystal polystyrene. Today, some 60% of polystyrene is of the impact-resistant type. The technical improvement involved numerous details it was necessary to learn how to handle highly viscous polymer melts, how to construct reactors for optimum removal of the reaction heat, how to remove residual monomer and solvents, and how to convey and meter melts and mix them with auxiliaries (antioxidants, antistatics, mold-release agents and colorants). All this was necessary to obtain not only an efficiently operating process but also uniform quality products differentiated to meet the requirements of various fields of application. In the meantime this process has attained technical maturity over the years it has been modified a number of times (Shell in 1966 (36), BASF in 1968 (37), Granada Plastics in 1970 (38) and Monsanto in 1975 (39)) but the basic concept has been retained. 

---