Synthesis and in vitro biological evaluations of novel tetrapeptide as therapeutic agent for wound treatment

• Main Authors: Nur Izzah Md Fadilah, Haslina Ahmad, Mohd Basyaruddin Abdul Rahman, Suet Lin Chia, Shiow-Fern Ng, Sze Wei Leong
• Format: Article
• Language: English
• Published: Elsevier 2020-08-01
• Series: Journal of Saudi Chemical Society
• Subjects: Tetrapeptide; Therapeutic agent; Cytotoxicity; Cell proliferation; Cell migration; Wound healing
• Online Access: http://www.sciencedirect.com/science/article/pii/S1319610320300788

We report a new small peptide containing four amino acid residues (glycine-aspartic acid-proline-histidine) conjugated with palmitic acid (Palmitoyl-GDPH) that was synthesized, characterized and evaluated for its biological activities. The Palmitoyl-GDPH was prepared by solid phase peptide synthesis (SPPS) with high percentage purity of 98.6%. The results of circular dichroism (CD) demonstrated the feasibility and stability of Palmitoyl-GDPH secondary structure at many temperatures up to 60 °C. Palmitoyl-GDPH showed its greatest collagenase inhibition activity and nitric oxide (NO) scavenging effect of 80.00 ± 2.22% at 1.0 mg/ml and 83.40 ± 8.08% at 2.5 mg/ml, respectively. In addition, in-vitro cell based study revealed that Palmitoyl-GDPH was not toxic and possessed strong proliferative activity towards normal human dermal fibroblast (NHDF) cell line. Wound scratch assay method showed that Palmitoyl-GDPH significantly promoted the cell migration which progressed faster compared to tetracycline-treated group (positive control) by about 98.39 ± 2.79% and 95.79 ± 3.83%, respectively. Collectively, these results suggested that newly synthesized Palmitoyl-GDPH possessed a strong candidate for use as therapeutic agent and can be a novel approach in the treatment of cutaneous wounds.