A Dde resin based strategy for inverse solid-phase synthesis of amino terminated peptides, peptide mimetics and protected peptide intermediates. |
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Authors: | Aman Rai William G Gutheil |
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Affiliation: | Department of Pharmaceutical Sciences, University of Missouri-Kansas City, 5005 Rockhill Road, Kansas City, Missouri 64110-2265, USA. |
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Abstract: | This report describes a Dde resin based attachment strategy for inverse solid-phase peptide synthesis (ISPPS). This attachment strategy can be used for the synthesis of amino terminated peptides with side chains and the carboxyl terminus either protected or deprotected. Amino acid t-butyl esters were attached through their free amino group to the Dde resin. The t-butyl carboxyl protecting group was removed by 50% TFA, and inverse peptide synthesis cycles performed using an HATU/TMP based coupling method. Protected peptides were cleaved from the resin with dilute hydrazine. Side chain protecting groups could then be removed by treatment with TFMSA/TFA. The potential of this approach was demonstrated by the synthesis of several short protected and unprotected peptides in good yield and with low epimerization. Its potential for peptide mimetic synthesis was demonstrated by the synthesis of two peptide trifluoromethylketones. |
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Keywords: | inverse solid‐phase peptide synthesis Dde resin peptide mimetic peptide trifluoromethylketone amino acid t‐butyl esters protected peptide fragment |
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