Skip to main page content
U.S. flag

An official website of the United States government

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2016 Jun 30;17(7):1023.
doi: 10.3390/ijms17071023.

Roles of d-Amino Acids on the Bioactivity of Host Defense Peptides

Hao Li  1 , Nuttapat Anuwongcharoen  2 , Aijaz Ahmad Malik  3 , Virapong Prachayasittikul  4 , Jarl E S Wikberg  5 , Chanin Nantasenamat  6
Affiliations
Review

Roles of d-Amino Acids on the Bioactivity of Host Defense Peptides

Hao Li et al. Int J Mol Sci. .

Abstract

Host defense peptides (HDPs) are positively-charged and amphipathic components of the innate immune system that have demonstrated great potential to become the next generation of broad spectrum therapeutic agents effective against a vast array of pathogens and tumor. As such, many approaches have been taken to improve the therapeutic efficacy of HDPs. Amongst these methods, the incorporation of d-amino acids (d-AA) is an approach that has demonstrated consistent success in improving HDPs. Although, virtually all HDP review articles briefly mentioned about the role of d-AA, however it is rather surprising that no systematic review specifically dedicated to this topic exists. Given the impact that d-AA incorporation has on HDPs, this review aims to fill that void with a systematic discussion of the impact of d-AA on HDPs.

Keywords: ">d-amino acid; AMP; HDP; anticancer peptide; antimicrobial peptide; bioactivity; diastereomer; host defense peptide.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Three-dimensional structure (A) and primary sequence (B) of Gramicidin D. The first panel shows the protein structure (PDB 1MAG) as a cartoon representation with d-AA shown as grey colored ball-and-sticks. As for the second panel, residues at the first position are represented by purple colored X that can be either valine or isoleucine. Furthermore, l- and d-AA are represented by black and red colored text, respectively, whereas the residue distinguishing the subtype of Gramidicin is indicated by the blue colored text.
Figure 2
Figure 2
Membrane interaction schematic of diastereomer and all-l peptides with zwitterionic and negatively-charged membranes. Step I: both types of HDP bind to membranes via the electrostatic force, and in the case of all-l peptides, a hydrophobic interaction is also present. Step II: increasing the peptide concentration will result in different outcomes depending on the peptide and membrane type. (A) Diastereomer interaction with a zwitterionic phosphatidylcholine and cholesterol (PC/Cho) membrane. The peptide remains at the surface and does not disrupt the membrane structure significantly; (B) The carpet mechanism, the primary diastereomer interaction pathway with the negative phosphatidylethanolamine and phosphatidylglycerol (PE/PG) membrane. A large number of the peptides engulf the membrane like a carpet, and their amphipathicity induces micellization. Toroidal pores may also be formed; (C) Partial carpet mechanism, the primary interaction mechanism of all-l host defense peptides (HDPs). This mechanism can occur when disrupting both negative and neutral membranes. Both the carpet and membrane pore disruption mechanisms occur. The partial carpet mechanism is also employed by strong hemolytic peptides, such as pardaxin, during the disruption of negative PE/PG membranes; (D) Barrel-stave mechanism, the mechanism employed by strong hemolytic HDPs, such as pardaxin, for the disruption of zwitterionic PC/Cho membranes. The peptides insert deep into the hydrophobic core of the membrane and form well-defined trans-membrane ion channel, with the peptide hydrophobic face facing the membrane hydrophobic core and the polar face facing inward. Adapted with permission from [49]. Copyright (2004) American Chemical Society.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Wang G., Hanke M.L., Mishra B., Lushnikova T., Heim C.E., Thomas V.C., Bayles K.W., Kielian T. Transformation of human cathelicidin LL-37 into selective, stable, and potent antimicrobial compounds. ACS Chem. Biol. 2014;9:1997–2002. doi: 10.1021/cb500475y. - DOI - PMC - PubMed
    1. Hilchie A.L., Doucette C.D., Pinto D.M., Patrzykat A., Douglas S., Hoskin D.W. Pleurocidin-family cationic antimicrobial peptides are cytolytic for breast carcinoma cells and prevent growth of tumor xenografts. Breast Cancer Res. 2011;13:1–16. doi: 10.1186/bcr3043. - DOI - PMC - PubMed
    1. Wang P., Nan Y.H., Shin S.Y. Candidacidal mechanism of a Leu/Lys-rich α-helical amphipathic model antimicrobial peptide and its diastereomer composed of d,l-amino acids. J. Pept. Sci. 2010;16:601–606. doi: 10.1002/psc.1268. - DOI - PubMed
    1. Lynn M.A., Kindrachuk J., Marr A.K., Jenssen H., Pante N., Elliott M.R., Napper S., Hancock R.E., McMaster W.R. Effect of BMAP-28 antimicrobial peptides on Leishmania major promastigote and amastigote growth: Role of leishmanolysin in parasite survival. PLoS Negl. Trop. Dis. 2011;5:1–13. doi: 10.1371/journal.pntd.0001141. - DOI - PMC - PubMed
    1. Hong W., Li T., Song Y., Zhang R., Zeng Z., Han S., Zhang X., Wu Y., Li W., Cao Z. Inhibitory activity and mechanism of two scorpion venom peptides against herpes simplex virus type 1. Antivir. Res. 2014;102:1–10. doi: 10.1016/j.antiviral.2013.11.013. - DOI - PMC - PubMed

MeSH terms