| Summary: | Protecting groups of the N<SUP>ε</SUP> animo function of lysine, which are removable under reductive conditions, have been investigated. The development of a lysine Nε </SUP> animo protecting group, compatible with the base labile N<SUP>α</SUP> amino protection strategy of peptide synthesis, is described. The protecting group, based on phenylacetic acid, is cleaved by the enzyme Penicillin Acylase (E.C.3.5.1.11) under very mild conditions. It has been demonstrated that the protecting group is stable to the conditions required for azide fragment condensation strategy. The group has been used to protect the N<SUP>ε</SUP> function of various lysine containing N<SUP>α</SUP> peptide hydrazides and azides. The potential of this protecting group with respect to the fragment condensation approach to polypeptide synthesis has been demonstrated in the preparation of the natural product, Salmon Calcitonin I. Modification of the protecting group has been shown to impart greater solubility to the protected peptide and also results in a substrate which is hydrolysed at a faster rate by the enzyme. Further modifications to the protecting group are proposed, together with the tailoring of the enzyme active site to a desired substrate.
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