Abstract
Human cathelicidin antimicrobial peptide LL-37 (LL-37) is an antimicrobial peptide derived from its precursor protein hCAP18, which is an only cathelicidin in human. LL-37 not only serves as a mediator of innate immune defense against invading microorganisms, but it also plays an essential role in tissue homeostasis, regenerative processes, regulation of proinflammatory responses, and inhibition of cancer progression. Therefore, LL-37 has been considered as a drug lead for diseases. However, high levels of LL-37 may reduce cell viability and promote apoptosis of osteoblasts, vascular smooth muscle cells, periodontal ligament cells, neutrophils, airway epithelial cells and T cells. Recent evidence reveals that LL-37-derived short peptides possess similar biological activities as the whole LL-37 with reduced cytotoxicity. Thus, such small molecules constitute a pool of potential therapeutic agents for diseases.
Highlights
The therapeutic application of LL-37 is limited due to its low cell selectivity and high production cost due to its large size [17]
This review describes advances in the development of LL-37derived short peptides for future therapeutics
The mature LL-37 has been shown to be degraded to shorter peptic fragments, including RK-31, KS-30 and KR-20 [29] by two distinct kallikreins: kallikrein 5 and kallikrein 7 [27, 30]. These natural and recently developed synthetic LL-37-derived short peptides have contributed to a better understanding of the full LL-37 peptide and the replacement for LL-37 to apply in treatment of diseases [31]
Summary
The precursor protein hCAP18 of LL-37 is composed of three parts: A N-terminal signal peptide, a highly conserved cathelin like domain, and an antimicrobial peptide domain at the C-terminus [21,22,23]. HCAP-18 in seminal plasma is cleaved by prostate-derived gastricsin to release a 38-amino acid antimicrobial peptide, ALL-38. The mature LL-37 has been shown to be degraded to shorter peptic fragments, including RK-31, KS-30 and KR-20 [29] by two distinct kallikreins: kallikrein 5 and kallikrein 7 [27, 30]. These natural and recently developed synthetic LL-37-derived short peptides have contributed to a better understanding of the full LL-37 peptide and the replacement for LL-37 to apply in treatment of diseases [31].
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