Biological and Medicinal Chemistry

Conjugation of proapoptotic peptides with folate and cyanine dyes for enhanced potency and selectivity towards tumor cell lines



Despite continuous advances, anticancer therapy still faces several technical hurdles such as selectivity on cellular and subcellular targets of therapeutics. Toward addressing these limitations, we have combined the use of proapoptotic peptides, cyanine dyes and folate to target the mitochondria of tumor cells. Hence, a series of proapoptotic peptides and their conjugates with a cyanine dye and/or a folate were prepared via solid-phase peptide synthesis (SPPS) and their activity tested in different mammalian cell lines. Compounds bearing either a cyanine dye or folate were found to be more cytotoxic than the parent peptides or more selective towards cells overexpressing the folate receptor α, which is commonly found on the surface of tumor cells. Nevertheless, constructs containing both components showed diminished potency and selectivity.


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Supplementary material

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Supporting Information
• SPPS procedures for compounds 3–15; TIC chromatograms of the crude of compound 3 synthesis before and after optimizing the SPPS protocol (Figure S1); TIC chromatogram of the crude for the synthesis of compound 10 after coupling folate to the ε-amino group of the N-terminal lysine. (Figure S2); TIC chromatogram of the crude of synthesis for compound 15 after coupling and deprotection of glutamic acid to the ε-amino group of the N-terminal lysine (Figure S3); characterization data for compounds 3–15 (Table S1 + Figure S4–S16); cytotoxicity data (Figure S17–S19). (PDF)