Linear Peptide Analogues from Jatropha’s Orbitides Promote Migration of Human Neonatal Foreskin Fibroblasts in vitro and Collagen Deposition

Suelem Ramalho,Meri Emili Pinto,Renata Andricopulo,Edilberto Silveira,Vanderlan Bolzani,Adriano Andricopulo,Eduardo Cilli,Paulo Sanches

doi:10.21577/0103-5053.20190102

Abstract

Orbitides are a class of small naturally occurring cyclic peptides with structural and functional diversities. Their chemical properties make this class feasible to be obtained by solid phase peptide synthesis (SPPS). Therefore, this synthetic accessibility enables useful application and facilitates the identification of analogues, bioactivity studies, and thus, enables them to be applied to obtain peptide libraries. The aim of this work was to investigate the effects of orbitides and their linear synthetic analogues on the migration of neonatal human foreskin fibroblasts. The screening of linear peptide analogues, originally designed from natural orbitides isolated from Jatropha species, demonstrated that some molecules (linear pohlianin B and linear ribifolin) have the potential to induce fibroblast migration and collagen deposition and may thus contribute to accelerating the processes of wound healing and tissue repair. These results also demonstrate the significance of using peptides as an important tool for the discovery of simple and novel drug scaffolds.

Highlights

Peptides play an important role in many cellular processes in living organisms, including plants
The latex from the Jatropha plant species is usually characterized as the main source of orbitides, which are accumulated in other parts of the plant such as the leaves, roots and stem bark
The studies demonstrate the significance of using natural products as starting points for the generation of simple and novel drug scaffolds. These data report for the first time the involvement of synthetic linear peptides in the processes of cell migration in human neonatal foreskin fibroblasts

Summary

Introduction

Peptides play an important role in many cellular processes in living organisms, including plants. Orbitides are plant-derived cyclic peptides with low molecular weight that have a ribosomally synthesized sequence of 5 to 12 amino acids, a lack of disulfide bonds and head-tail cyclization as a post‐translational modification. They have been documented in families including Annonaceae, Euphorbiaceae, Lamiaceae, Linaceae, Phytolaccaceae, Rutaceae, Schizandraceae and Verbenaceae.. Highlighting the importance of structural diversity, solid phase peptide synthesis (SPPS) is a convenient and useful approach to obtain peptide analogues; this method allows molecules with chemo‐diversity to be obtained in appropriate amounts, helping to drive their applications as drug scaffolds.10,11 In plants, they are usually produced in minimal yield Highlighting the importance of structural diversity, solid phase peptide synthesis (SPPS) is a convenient and useful approach to obtain peptide analogues; this method allows molecules with chemo‐diversity to be obtained in appropriate amounts, helping to drive their applications as drug scaffolds. In plants, they are usually produced in minimal yield

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