De novo design of antiviral and antibacterial peptides with varying loop structures

Guangshun Wang, Karen W. Buckheit, Biswajit Mishra, Tamara Lushnikova, Robert W. Buckheit

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Although the rate of new HIV infections has been declining, AIDS continues to be one of the leading causes of death worldwide. The lack of an effective HIV vaccine makes it necessary to develop alternative strategies, such as the development of topical microbicides, to prevent transmission. Antimicrobial peptides represent promising microbicide candidates. Previously, we succeeded in enhancing the anti-HIV activities of several peptides that form helical structures based on the bioinformatic results learned from the antimicrobial peptide database. This study showed that Lys-to-Arg alterations also improved the HIV inhibitory activity of thanatin which is known to form a β-hairpin structure. Using a previously reported de novo designed HIV inhibitory peptide GLR-19 as the starting template, loop structures of varying sizes were generated by restraining a disulfide bond at different positions. The thanatin-mimicking constructs are referred to as GLRC peptides since they are composed of only four amino acid residues G, L, R, and C. While GLRC-2, the peptide with a medium-sized loop structure, was most potent against HIV-1 and HSV-2, GLRC-3, with the small loop structure, was most potent against Escherichia coli K12. Thus, the efficacy of the GLRC peptides is microbe dependent. Further terminal sequence truncation of GLRC-2 reduced antimicrobial activity against both viruses and bacteria. It appears that the high antiviral potency of GLRC-2 is related to high hydrophobicity, although a wide-range correlation is lacking. In addition, GLRC-2, which is more active against viruses, is also more resistant to the action of chymotrypsin. Therefore, GLRC-2, a novel peptide that acquired not only higher stability but also higher anti-HIV activity than the GLR-19 template, serves as the starting point for additional rounds of peptide engineering.

Original languageEnglish (US)
JournalJournal of AIDS and Clinical Research
Volume3
Issue numberSPL ISSUE2
DOIs
StatePublished - Dec 1 2012

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Keywords

  • Antimicrobial peptides
  • HIV-1
  • Microbicides
  • Peptide stability

ASJC Scopus subject areas

  • Immunology
  • Dermatology
  • Infectious Diseases
  • Virology

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