Sulfhydryl group, alkylation

As seen in Figure 1, the organo sulfur compounds are methylated at the boiling point (90°C) of dimethyl carbonate, whereas methylation (or alkylation with other alkyl groups) of other functional groups requites higher temperatures. This has resulted in the selective methylation of sulfhydryl groups of compounds that contain other substituents that can be alkylated. The other substituents can then be alkylated at elevated temperatures (63). 

Warfarin, diphenacoum, bromodiolone, flocoumafen, and brodiphacoum are examples Both alkyl and aryl mercury compounds can bind to sulfhydryl groups Have caused population declines in certain mollusks... 

Figure 1.10 Sulfhydryl groups may undergo a number of additional reactions, including acylation and alkylation. Thiols also may participate in redox reactions, which generate reversible disulfide linkages.

Maleic acid imides (maleimides) are derivatives of the reaction of maleic anhydride and ammonia or primary amine compounds. The double bond of a maleimide may undergo an alkylation reaction with a sulfhydryl group to form a stable thioether bond (Chapter 2, Section 2.2). Maleic anhydride may presumably undergo the same reaction with cysteine residues and other sulfhydryl compounds. 

PROTECTION OF CARBOXYL, HYDROXYL, AND SULFHYDRYL GROUPS BY TFRT-BUTYLATION AND ALKYLATION... 

Castro, J.A. Effects of alkylating agents on human plasma cholinesterase The role of sulfhydryl groups In its active center. Biochem. Pharmacol. 17 295-303, 1968. 

The 2-chloroacetanilides (Figure 2.22) are also suggested to inhibit cell division in susceptible weeds. These compounds have found a major commercial market for the pre-emergence control of grass and some small seeded broad-leaved weeds in crops such as maize and soybean. It is likely that 2-chloroacetanilides also alkylate the sulfhydryl groups of certain essential plant enzymes. 

In addition to the alkylation with iodoacetate (Eq. 3-24), sulfhydryl groups can react with N-ethylmale-imide (Eq. 3-39).281 This reaction blocks the SH groups irreversibly and has often been used in attempts to establish whether or not a thiol group plays a role in the functioning of a protein. Loss of function in the... 

The ricin and abnn A chains used to block high affinity binding sites on the column should be alkylated to remove the free sulfhydryl group that could interfere with conjugate purification... 

Further structure-activity relationship (S AR) analyses of other cytoprotective enzyme inducers revealed the fact that all inducers can react with thiol/disulfide groups by alkylation, oxidoreduction, or thiol-disulfide interchange [Dinkova-Kostova and Talalay, 1999]. In fact, the capability of enzyme inducers to induce cytoprotective enzymes is well correlated with their reactivity with thiols. These results suggested a cellular sensor of inducers with highly reactive sulfhydryl groups, possibly reactive thiols in cysteine residues of a sensor protein. Nevertheless, the initial search for the sensor protein by using radioactively labeled inducers was not successful due to the abundance of thiol groups presented in many proteins in cells [Holtzclaw et al., 2004]. The molecular mechanism by which cytoprotective enzymes are induced remained to be elucidated. 

Cysteine proteinase contain a catalytic ally active cysteine snUhy ljtQup (Cys-25) and a histidine group (His-i59) within the active center of the sizyme [51]. Alkylation of the active-center sulfhydryl group renders the product inactive. The minimal reaction mechanism is represented in Figure 4 [52]. 

Ketone 2 and its metabolite chloro-acetone (16) are alkylating agents. This property is of special importance, when the substrate is being reduced stereoselectively by reductases with an essential sulfhydryl function. Because the sulfhydryl groups are inhibited irreversibly by alkylation [69], stereoisomer distribution in the product is considerably affected. 

However, if a reagent would react only with a single site on a macromolecule, then a chemically homogeneous product having one chelator per protein molecule could be formed. Alkylation of the single sulfhydryl group of albumin with a haloacetyl reagent probably comes reasonably close to this situation. 

Examination of the three-dimensional structure of papain (Lab Quip) indicated that because of the extended groove present in the vicinity of the active site residue Cys-25, it should be feasible to alkylate the sulfhydryl group with a coenzyme analog, still permitting the binding of potential substrates. 

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