Protected peptides solubility

An alternative and possibly more simple approach to S-prenylation is based on S-alkylation of suitably protected or unprotected peptides. This method is widely applied particularly when small amounts of S-prenylated peptides are required, whereby preparative RP-HPLC is generally applied for the isolation of the lipopeptides. The S-alkylation methods used are generally those described above. Whilst with suitably protected peptides solubility represents a major problem, which can be bypassed by S-alkylation of the peptide on resin, 61 with unprotected peptides a very efficient tuning of the reaction conditions is required... 

Oh-Uchi SK, Yang JY, LeeJS, MurakawaY, and Narita M. Only Weak Dependence of the Protected Peptides Solubility in Organic Solvent on their Amino Acid Sequence. Polym/1996 28 1033-1038. 

Correlation of protected peptide solubility in solution with structure (32, 48,49) ... 

The p nitrophenol formed as a byproduct in this reaction is easily removed by extrac tion with dilute aqueous base Unlike free ammo acids and peptides protected peptides are not zwitteriomc and are more soluble m organic solvents than m water... 

J Bodi, H Nishio, T Inui, Y Nishiuchi, T Kimura, S Sakakibara. Segment condensation of sparingly soluble protected peptides in chloroform-phenol mixed solvent, in S Bajusz, F Hudecz, eds. Peptides 1998. Proceedings of the 25th European Peptide Symposium. Akademiai Kiado, Budapest, 1999, pp 198-199. 

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. 

Poor peptide solubility has been identified as a major obstacle to efficient segment assembly of peptides on a solid phase particularly for fully protected strategies. 1,5,6 Backbone protection directly addresses this problem and is the basis for a general route to the synthesis of small proteins. 7,8 However, the inclusion of backbone protection in a synthesis is not yet automated or routine and requires careful planning. 

Minimally protected peptides (restricted to amino group protection) allow for high solubility and reactivity during cross-linking. 

Aminomethyl-3-nitrobenzoylpolyethyleneglycols are another class of photosensitive soluble polymeric supports designed for the liquid phase synthesis of protected peptide amides 192,193) (scheme 8). These supports have been very recently used for efficient synthesis of three biologically active 14-peptideamides corresponding to the wasp venom peptides, mastoparan, mastoparan X and Polistes mastoparan 198). 

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