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Proteases play a key role in literally all biological processes, and are of great interest to the pharmaceutical industry. Peptide-7-amino-4-methylcoumarin conjugates (peptide-AMCs) have been widely used as fluorogenic substrates to study biological behaviors of proteases. The preparation of peptide-AMCs usually involves additional synthetic steps in solution phase, because 7-amino-4-methylcoumarin (AMC) lacks an additional functional group for attachment to a solid support. To address this issue, solid-phase synthetic strategies using a backbone amide linker (BAL linker) or the side chain functionality of the C-terminal amino acid as an anchor point have been developed. However, both of the approaches require solution-phase synthesis of amino acid-AMC conjugates, and the latter is not applicable to the majority of amino acids. Solid-phase synthesis of peptide-7-amino-4-carbamoylmethylcoumarin conjugates (peptide-ACCs) as an alternative for peptide-AMCs has also been reported.In the present study, we have developed a novel solid support, namely, AMC-resin, for facile solid-phase synthesis of peptide-AMCs. In this synthetic methodology, 7-N (Fluorenylmethoxycarbonyl)aminocoumarin-4-acetic acid (Fmoc-Aca-OH) is attached to Wang resin as a linker. After removal of the N-fluorenylmethoxycarbonyl (Fmoc) protecting group, peptides are synthesized on the amino group of the linker using standard Fmoc-chemistry, followed by cleavage with trifluoroacetic acid. The crude peptide-7-aminocoumarin-4-acetic acid conjugates (peptide-ACAs) undergo facile decarboxylation under mild condition to afford peptide-AMCs. The utility and versatility of this approach were demonstrated by synthesis of sample peptide-AMCs, e.g. Z-DEVD-AMC and Ac-EEVVAC-AMC. The desired peptide-AMCs were obtained in good yield and crude purity. Side chain functionalities of amino acids such as cysteine and arginine were well tolerated. This approach is straightforward and versatile, and is ideally suited for combinatorial synthesis of peptide-AMCs. We anticipate that the AMC-resin will greatly facilitate the synthesis of peptide-AMCs as fluorogenic substrates for proteases.