Abstract
Here we report the synthesis and effect on the cell viability of pyrrole-conjugated phosphopeptides. Encouraged by the selective inhibition of cancer cells by a naphthyl-capped phosphopeptide (Nap-ffpy, 1), we conjugated the heteroaromatic dipyrrole or tripyrrole motif at the N-terminal of short peptides containing phosphotyrosine or phosphoserine and examined the bioactivity of the resulting phosphopeptides (2–10). Although most of the phosphopeptides exhibit comparable activities with that of 1 against HeLa cells at 200 μM, they, differing from 1, are largely compatible with HeLa cells at 400 μM. Enzymatic dephosphorylation of 2–10, at 400 μM is unable to induce a dramatic morphological transition of the peptide assemblies observed in the case of 1. These results suggest that a heteroaromatic motif at the N-terminal of peptides likely disfavors the formation of extensive nanofibers or morphological changes during enzymatic self-assembly, thus provide useful insights for the development of phosphopeptides as substrates of phosphatases for controlling cell fate.
Highlights
Biomacromolecular assemblies have received considerable attention recently in the field of biomaterials [1,2,3,4,5,6,7], among which peptides are of particular interest because of their unique merits, such as ease of design and tailoring, good biocompatibility and degradability, and low immunogenicity
One of the most explored enzyme-instructed self-assembly (EISA) processes is the use of alkaline phosphatase (ALP) to convert the micelles made of phosphopeptides to the nanofibers of peptides via enzymatic dephosphorylation [20,60]
2–10 at 400 μM, differing drastically from 1, are largely compatible with HeLa cells, while 1, at 400 μM, significantly inhibits HeLa cells. These results suggest that morphological transition or extensive selfassembly triggered by enzymatic reactions likely is necessary for the inhibition of HeLa cells by EISA
Summary
Biomacromolecular assemblies have received considerable attention recently in the field of biomaterials [1,2,3,4,5,6,7], among which peptides are of particular interest because of their unique merits, such as ease of design and tailoring (based on the known structures from proteins), good biocompatibility and degradability, and low immunogenicity. One of the most explored EISA processes is the use of alkaline phosphatase (ALP) to convert the micelles made of phosphopeptides to the nanofibers of peptides via enzymatic dephosphorylation [20,60]. While ALP-catalyzed EISA has received considerable exploration, the structures of the peptide substrates mainly have centered on naphthylacetyl-capped phosphopeptides (e.g., Nap-ffpy (1)) [36,61,62,63,64,65,66].
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