Design and Synthesis of Multidetachable Resin Supports for Solid-Phase Peptide Synthesis

Article abstract of DOI:10.1021/ja00539a025

A new and unusually versatile class of supports for solid-phase peptide synthesis has been developed.It contains two orthogonally removable ester bonds, allowing the selective cleavage of the individual bonds by a variety of reagents.The synthetic peptide can be obtained in a free or protected form, or with a removable spacer group still attached at the carboxyl terminus.Two such multidetachable resin supports have been developed in which selective cleavage is by acidolysis, photolysis, or nucleophilic cleavage; they are (1) tert-butoxycarbonylaminoacyl-2-<4-(oxymethyl)phenylacetoxy>propionyl-copoly(styrene-divinylbenzene) resin (Pop-resin) and tert-butoxycarbonylaminoacyl-4-<4-(oxymethyl)phenylacetoxymethyl>-3-nitrobenzamidomethyl-copoly(styrene-divinylbenzene) resin (Pon-resin).The value of these resins was demonstrated by the stepwise synthesis of Leu-enkephalin and angiotensin II.In addition, applications of this class of supports for fragment synthesis were described.The minimization of side reactions associated with peptide anchored to photolabile resins in the ordinary way was demonstrated.