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

Abstract

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.

Controllably Self-Assembled Antibacterial Nanofibrils Based on Insect Cuticle Protein for Infectious Wound Healing

“…Inspired by the above antibacterial ability, animal studies were conducted to assess the efficacy of Of CPH-2 in the treatment of infectious wounds. First, Sprague−Dawley rats (SD rats) were randomly divided into the following four groups: the negative control group, the Of CPH-2 group, the vancomycin group (positive control), and the human epidermal growth factor group (EGF, positive control, Figure S11). As shown in Figure S11A, S. Aureus (ATCC 29213) was administered to rats on day 0 to establish an infectious wound model.…”

Identification of Micrococcin P2-Derivatives as Antibiotic Candidates against Two Gram-Positive Pathogens

“…Additionally, 6c was found to downregulate pro-inflammatory cytokines such as IL-6 and IL-1β, which are known to exacerbate clinical symptoms of impetigo and promote bacterial survival through the formation of biofilms. 66,67 We speculate that the superior in vivo activity of 6c can be attributed to its dual actions on bacteria and the host immune system. While the latter aspect requires further investigation, 6c was ultimately selected as an ideal preclinical candidate for impetigo.…”

A Systematic Review of the Design and Applications of Antimicrobial Peptides in Wound Healing

“…Chol-37(F34-R), a new wound-healing AMP, was developed utilizing PMAP-37 as a template [ 66 ]. In a similar vein, AMP Human hemokinin-1 served as the foundation for the creation of other AMPs, including AH-4 [ 69 ]. The novel AMP FWKFK was manufactured using Fmoc chemistry, and the product was tested using modified cell membrane chromatography [ 71 ].…”

“…In a variety of wound types, including diabetic and Staphylococcus aureus -infected animals, the effectiveness of AH-4 in wound healing has been shown. Significant wound-healing activity was shown by AH-4, and there was no discernible variation in effectiveness at varied doses [ 69 ]. AH-4 not only averted bacterial infection but also markedly boosted wound closure in a wound model infected with bacteria, unlike vancomycin, which only illustrated the antibacterial effect [ 69 ].…”

“…Significant wound-healing activity was shown by AH-4, and there was no discernible variation in effectiveness at varied doses [ 69 ]. AH-4 not only averted bacterial infection but also markedly boosted wound closure in a wound model infected with bacteria, unlike vancomycin, which only illustrated the antibacterial effect [ 69 ]. Furthermore, in contrast to the control group, AH-4 revealed a substantial rise in wound healing in the diabetic mouse model, implying that it has substantial therapeutic potential for the management of diabetic wound healing [ 69 ].…”