Synthesis and bioactivity of pyrrole-conjugated phosphopeptides

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.

Exploring Supramolecular Interactions between the Extracellular-Matrix-Derived Minimalist Bioactive Peptide and Nanofibrillar Cellulose for the Development of an Advanced Biomolecular Scaffold

“…However, recently, few studies in the literature have raised concerns regarding the long-term biocompatibility of the “fmoc” group toward cells. − Some of the recent studies have also suggested the need to choose some alternative aromatic groups to “fmoc” to enhance the biocompatibility of the designer peptide hydrogels. , In this context, various other N-terminal capping groups to induce the self-assembly of short peptides have been explored . Napthoxyacetic acid being one among those alternate aromatic groups has been extensively reported in the literature. ,,, In our previous studies, we have reported that the Nap moiety containing hydrogel scaffolds, e.g., Nap-FFGSO, Nap-IKVAV, and Nap-YIGSR, have shown significant biocompatibility as well as potential to support 2D cell culture of different types of cells in hydrogel form . In the literature, various other designs have also been proposed to induce the self-assembly of designer short peptide amphiphiles. , One of the most popular approaches is capping the bioactive peptide with an aliphatic chain to design self-assembling peptide amphiphiles .…”

“…It is worth mentioning that aromatic group capped peptides have been extensively used in the literature to develop biomimetic scaffolds for tissue engineering applications . However, recently, few studies in the literature have raised concerns regarding the long-term biocompatibility of the “fmoc” group toward cells. − Some of the recent studies have also suggested the need to choose some alternative aromatic groups to “fmoc” to enhance the biocompatibility of the designer peptide hydrogels. , In this context, various other N-terminal capping groups to induce the self-assembly of short peptides have been explored . Napthoxyacetic acid being one among those alternate aromatic groups has been extensively reported in the literature. ,,, In our previous studies, we have reported that the Nap moiety containing hydrogel scaffolds, e.g., Nap-FFGSO, Nap-IKVAV, and Nap-YIGSR, have shown significant biocompatibility as well as potential to support 2D cell culture of different types of cells in hydrogel form .…”

“…68 Napthoxyacetic acid being one among those alternate aromatic groups has been extensively reported in the literature. 11,13,70,71 In our previous studies, we have reported that the Nap moiety containing hydrogel scaffolds, e.g., Nap-FFGSO, Nap-IKVAV, and Nap-YIGSR, have shown significant biocompatibility as well as potential to support 2D cell culture of different types of cells in hydrogel form. 10 In the literature, various other designs have also been proposed to induce the self-assembly of designer short peptide amphiphiles.…”

“…67−69 Some of the recent studies have also suggested the need to choose some alternative aromatic groups to "fmoc" to enhance the biocompatibility of the designer peptide hydrogels. 68,70 In this context, various other N-terminal capping groups to induce the self-assembly of short peptides have been explored. 68 Napthoxyacetic acid being one among those alternate aromatic groups has been extensively reported in the literature.…”