Peptide fragment, fully protected

It has long been recognized that fragment condensation on a solid phase would be highly desirable. 1,5,6 However, the solid-phase fragment coupling approach has been limited by the notoriously poor solubility properties of fully protected peptides that make them difficult to purify and characterize. 

Mergler, M. Nyfeler, R. Tanner, R. Gosteli, J. Grogg, P. Peptide Synthesis by a Combination of Solid-Phase and Solution Methods. 11. Synthesis of Fully Protected Peptide Fragments on 2-Methoxy-4-alkoxybenzyl Alcohol Resin, Tetrahedron Lett. 1988, 29,4009. 

Mergler, M., Nyfeler, R., Tanner, R., Gosteli, J., and Grogg, P. (1988) Peptide synthesis by a combination of solid-phase and solution methods II synthesis of fully protected peptide fragments on 2-methoxy-4-aIkoxy-benzyl alcohol resin, Tetrahedron Lett. 29, 4009—4012. 

Fig. l The use of the 2-chlorotrityl chloride resin for the preparation of protected peptides and proteins. Either amino acids (a) or fully protected peptide fragments (b) are condensed to the growing peptide chain on the resin. 

The synthesis of the N-acetyl-muramyl tetrapeptide (61) (33,44), which has the peptide sequence of the monomeric glycopeptide unit of many peptidoglycans, and that of its diastereoisomer (62) (45) has been reported. The fully protected tetrapeptide was prepared by coupling the two fragments BOC-L-Ala-D-isoGln and Lys(Z)-D-(or L)-Ala-OBzl by means of the mixed anhydride method. 

However, already in a minor excess of 50% the caesium salts not only of N-protected amino acids but di- and tripeptides under identical conditions completely react with bro-moacetyl groups on polymer, because of the enhanced electrophilic reactivity of those sites (Fig. 29) [85]. The phenacyl ester so formed are particularly suitable in experiments to synthesize fully protected peptide fragments, an aspect which will be discussed in Sect. 3.5. 

Peptides attached to resins 3, 4, 5, 7, 8, and 11 can be released under conditions that leave most standard side-chain protecting groups intact. These supports are therefore valuable tools for the preparation of fully protected peptides for use in fragment condensation or cyclization strategies. Peptide release is normally effected by repetitive treatment with 1% TFA in DCM for resins 5, 7, and 8 this can also be achieved under even milder conditions using TFE in DCM, as described in Chapter 9, Protocol 3. 

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