Development of Neuropeptide Hemokinin‑1 Analogues with Antimicrobial and Wound-Healing Activity

Wound healing is a complex process that can be delayed
in some
pathological conditions, such as infection and diabetes. Following
skin injury, the neuropeptide substance P (SP) is released from peripheral
neurons to promote wound healing by multiple mechanisms. Human hemokinin-1
(hHK-1) has been identified as an SP-like tachykinin peptide. Surprisingly,
hHK-1 shares similar structural features with antimicrobial peptides
(AMPs), but it does not display efficient antimicrobial activity.
Therefore, a series of hHK-1 analogues were designed and synthesized.
Among these analogues, AH-4 was found to display the greatest antimicrobial
activity against a broad spectrum of bacteria. Furthermore, AH-4 rapidly
killed bacteria by membrane disruption, similar to most AMPs. More
importantly, AH-4 showed favorable healing activity in all tested
mouse full-thickness excisional wound models. Overall, this study
suggests that the neuropeptide hHK-1 can be used as a desirable template
for developing promising therapeutics with multiple functions for
wound healing.