chapter  3
30 Pages

Acylating Agents

The acylation of proteins with long-chain fatty acids was mentioned earlier. The acylation of proteins with long-chain fatty acids can be an important posttranslational modication as shown in the coupling of myristic acid to amino-terminal glycine residue7,8 and coupling of palmitic acid to cysteine.9,10 The reversible coupling of palmitic acid to proteins is critical to transport and intracellular signaling.11,12 The reversible acetylation of lysine residues in proteins is also an important regulatory process.13-17 The process of in vivo acylation of proteins is likely more heterogeneous than originally described.18-20 The in vivo acylation and deacetylation of proteins is an enzymatic process involving acetyl coenzyme A.21 Thioesters are intermediates in native chemical ligation (Figure 3.6) and thioester peptides have been used in the synthesis of novel protein.22-25

Organic acid chlorides, such as acetyl chloride, are acyl halides and highly reactive.26 The reactivity is similar to that observed for the alkyl halides. Thus, the rate of hydrolysis of acetyl uoride in water/acetone (25/75) has a relative rate of 2.2 × 102 (benzenesulfonyl uoride has a rate of 1 in H2O/ acetone; 1/1); the relative rate of hydrolysis of acetyl chloride in water/acetone (25/75) is 1.7 × 107, while the relative rate for the hydrolysis of dimethylcarbamoyl chloride in water26 is 1.1 × 105. The high reactivity of the organic acid chlorides such as acetyl chloride provides little opportunity for selective modication; in fact, there is little application of acyl chlorides for the modication of

N­diphenylcarbamoyl chloride that modies the active-site serine in chymotrypsin.27