S-Acylation

Thioester (Section 20 13) An S acyl denvative of a thiol a compound of the type... 

Acylation of pyridazinethiones with acetyl chloride or benzoyl chloride gives the corresponding S-acylated products. 6-Mercaptopyridazine-3(2//)-thione gives either mono- or di-S-acylated products. A bispyridazinyl derivative is formed when phosgene or thiophos-gene is used as acylating agent. 

Pyrimidine-2-sulfonyl chloride, 4,6-dimethyl-reactions, 3, 97 Pyrimidinesulfonyl halides reactions, 3, 97 Pyrimidinethiols S-acylation, 3, 95 S-alkylation, 3, 94 oxidation, 3, 94 synthesis, 3, 135 Pyrimidine-5-thiols oxidation, 3, 94 synthesis, 3, 136... 

Synthesis of 2-(A-cyanoimino)thiazolidines and use of their 3-acyl derivatives as efficient N-, 0-, and S-acylating agents 98YGK182. 

S-acylated proteins include many GTP-binding regulatory proteins (G proteins), including most a subunits of heterotrimeric G-proteins and also many members of the Ras superfamily of monomeric G proteins, a number of G protein-coupled receptors, several nonreceptor tyrosine kinases, and a number of other signaling molecules, -acylation is posttranslational and reversible, a property that allows the cell to control... 

S-acyl (S-palmitoyl) 0 ii /WV VWVN S-Cys Cysteine, no defined consensus... 

An inverse addition of sulfinic acid to a thiocarbonyl group could have taken place with the reactive intermediate 8, which should arise from thiophosgene and methanesulfmic acid (sodium salt)106 (equation 28). The first step of this reaction represents an S-acylation... 

TABLE 2. Sulfones from S-acylations of sulfmate anions RSOz... 

Further interesting S-acylations have been reported for the synthesis of a cholesteryl thiolestertl76] (see also references [184] and [178]) or an azetidinoneacetic acid thiol-estertl84] by use of CDI, as well as of a thiolester with the deoxydaunomycinone structure by use of CDI and Mg(OC2H5)2.[186]... 

Despite the many simple methods for preparation of carboxylic esters and thioesters, in some instances, use of 1-acylbenzotriazoles 915 as O and S acylating agents may be advantageous. For example, easy to prepare salicylic acid derivative 941 reacts with cyclopentanol under microwave irradiation to give 92% yield of cyclopentyl salicylate in 10 min <2006JOC3364>. In another example, L-phenylalanine derivative 942 reacts with benzyl mercaptan... 

These findings led to the conclusion that the regulation of membrane anchored proteins has to be achieved by mechanisms other than spontaneous dissociation. In principal, binding to an escort protein or de-S-acylation may induce dissociation of the lipoproteins out of the membrane structure. 

In a related experiment CV-1 fibroblasts were incubated with fluorescent N-Ras lipopeptides bearing a free palmitoylation site. These peptides cause staining of the CV-1 plasma membrane and efficient S-acylation even if the farnesyl group was replaced by a n-octyl group.1271 The association of the N-Ras lipopeptides with the plasma membrane... 

S-Acylation and Plasma Membrane Targeting of the Farnesylated Carboxyl-Terminal Peptide of N-Ras in Mammalian Fibroblasts, H. Schroeder, R. Leventis, S. Rex, M. Schelhaas, E. Nagele, H. Waldmann, J. R. Silvius, Biochemistry 1997, 36,13102-13109. 

While acid chlorides react as shown in (123) thiocarbonyl chlorides, presumably because the C=S carbon is less electropositive, give S-acylation with sulfinates (125) (Senning et al., 1968 Nilsson et al., 1971). 

It is noteworthy that there is another limiting factor in the choice of amino acid types at the junction sites which affect the enzymatic process of the intein. For example, in the case of SceVMA (also called PI-Seel) from the IMPACT system, proline, cysteine, asparagine, aspartic acid, and arginine cannot be at the C-terminus of the N-terminal target protein just before the intein sequence. The presence of these residues at this position would either slow down the N-S acyl shift dramatically or lead to immediate hydrolysis of the product from the N-S acyl shift [66]. The compatibility of amino acid types at the proximal sites depends on the specific inteins and needs to be carefully considered during the design of the required expression vectors. The specific amino acid requirements at a particular splicing site depends on the specific intein used and is thus a crucial point in this approach. 

S. Benzaria, H. Pelicano, R. Johnson, G. Maury, J. L. Imbach, A. M. Aubertin, G. Obert, G. Gosselin, Synthesis, in vitro Antiviral Evaluation, and Stability Studies of Bis(S-acyl-2-thioethyl) Ester Derivatives of 9-[2-(Phosphonomethoxy)ethyl]adenine (PMEA) as Potential PMEA Prodrugs with Improved Oral Bioavailability , J. Med. Chem. 1996, 39, 4958-4965. 

The acylated peptides (Myr)GCX-Bimane 31 a-e (X = G, L, R, T, V), which are found in certain nonreceptor tyrosine kinases and ct-subunits of several heterotrimeric G-proteins, were synthesized in solution using common solution-phase peptide synthesis with X-myristoylglycine as a building block. These model peptides were used for acylation studies with palmitoyl-CoA in phospholipid vesicles at physiological pH. For such uncatalyzed spontaneous reactions only a modest molar excess of acyl donor species (2.5 1) was necessary. Unprotected side chains of threonine or serine are not interfering with this S-acylation (Scheme 14). 

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