Use of Hmb protection to increase solution solubility

Peptide insolubility occurs when the combined inter- and intrapeptide ionic and hydrophobic interactions outweigh favourable peptide-solvent interactions. 

FiguraT. HPLC profiles of total crude products from the assembly of decapeptide IV. (a) Standard assembly without backbone amide protection, (b) Introduction of (Hmb)Ala, no aggregation during remaining assembly. Conditions Aquapore RP-300 Cs (250 x 4.6 mm) 10-50% B in A linear gradient over 25 min, 1.5 ml/min, 215 nm UV detection, where solvent A = 0.1% aq. TFA and solvent B = 90% acetonitrile/10% solvent A. (Reproduced from ref. 60 with permission from The Royal Society of Chemistry.) 

The retention of Hmb backbone protection on fully protected peptide segments in solution also gives extraordinarily soluble materials (71, 72). Backbone-protected segments are readily purified by standard reverse-phase HPLC and subsequently couple smoothly and cleanly in either DMF or DCM due to the highly concentrated coupling solutions prepared. 

and Meienhofer, J. (ed.) (1981). TTie peptides, analysis, synthesis, biology, Vol. 3. Academic Press, New York. 

Atherton, E. and Sheppard, R. C. (1989). In Solid phase peptide synthesis a practical approach, p. 1. Oxford University Pr, UK. 

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