Acid-labile precursors

In this approach an orthogonal S-protection consisting of the acid-labile Mob and the Acm group was selected. Free thiol peptides were prepared by acid treatment of the precursors and activated with di(2-pyridyl) disulfide to afford the 5-SPy derivatives which served for the preparation of the two heterodimers 60 and 62 via thiolysis with a second cysteine peptide. In both heterodimers 60 and 62 the Acm group was cleaved with silver(I) trifluoroacetate in TFA to generate the mercaptide. Following gel filtration in acidic media the free thiol from 62 was activated as the S-SPy derivative 63 and subsequent thiolysis with the second heterodimer 61 in the free thiol form produced the heterotetramer 64. 

Hydrolytic Decomposition of Phosphoprotein. The kinetic analysis of phosphate liberation revealed that phosphate is not steadily liberated but that an initial lag period occurs which is followed by a transient burst of phosphate liberation123, 177> 192 This burst has been interpreted as resulting from the accumulation of an acid-labile intermediate arising from an acid-stable precursor. The burst is fol-... 

The perhydroxy radical formed on the y-carbon atom (Reactions 30 and 31) is a likely precursor of aspartic acid, which we have found in yields of G = 1.1 when PGA was irradiated in 0.1% solution in 02. Further oxidation and a decarboxylation step would be required to give aspartic acid. However, it is not yet known whether the aspartic acid is formed solely as a result of irradiation it may be formed from a labile precursor during acid hydrolysis of the polymer. Our results differ from those reported by Friedberg and Hayden, who found high yields of aspartic acid in PGA irradiated in the absence of 02 we found only traces of aspartic acid from solutions of PGA irradiated under N2 (Figure 3). Glycine formation was not affected by the presence of 02. 

Trityl-based resins are highly acid-labile. The steric hindrance of the linker prevents diketopiperazine formation and the resins are recommended for Pro and Gly C-terminal peptides. Extremely mild acidolysis conditions enable the cleavage of protected peptide segments from the resin. These resins are commercially available as their chloride or alcohol precursors. The trityl chloride resin is extremely moisture-sensitive, so reagents and glassware should be carefully dried before use to avoid hydrolysis into the alcohol form. It is necessary to activate the trityl alcohol precursor and it is highly recommended to reactivate the chloride just before use see Note 4). After activation, attachment of the first residue occurs by reaction with the Fmoc amino acid derivative in the presence of a base. This reaction does not involve an activated species, so it is free from epimerization. Special precautions should be taken for Cys and His residues that are particularly sensitive to epimerization during activation (Table 2). 

Cronin J. R. (1976a) Acid-labile amino acid precursors in the Murchison meteorite 1. Chromatographic fractionation. Origins Life 7, 337-342. 

According to animal studies (Swick and Benevenga, 1977), a labile protein reserve that can be gained or lost from the body for emergencies or to account for the day-to-day variations in dietary protein intake is contained in the liver and visceral tissues. Rapid starvation or dietary protein depletion results in a loss of the reserve by as much as 40%, while skeletal muscle drops much more slowly. Thus, protein breakdovm becomes the source of indispensable amino acids needed for synthesis of critical proteins necessary for body functions (Reeds et ah, 1994) and provides amino acids as precursors for energy production. 

Complex RCAM processes are mediated by both 2 and 3. The macrocycHc saUcylate lactone cruentaren A (36) has been prepared independently by two groups, Maier [37, 38] and Fiirstner [39], using a RCAM approach. Their chosen cyclization precursors, 34a and 34b, differ only by the choice of a particular silyl protecting group and in the extent of functionaHzation on the side chain (Scheme 7.13). Both RCAM processes could be performed in high yield. Complex 3/CH2CI2 had to be used for the cychzation of 34b, as its acid-labile OTHP functionahty was incompatible with complex 2. 

---